Acetylation: Formation of an acetyl derivative. (Stedman, 25th ed)Sirtuin 3: A sirtuin family member found primarily in MITOCHONDRIA. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.Histone Deacetylases: Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.Histone Deacetylase Inhibitors: Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.Histone Acetyltransferases: Enzymes that catalyze acyl group transfer from ACETYL-CoA to HISTONES forming CoA and acetyl-histones.Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1.p300-CBP Transcription Factors: A family of histone acetyltransferases that is structurally-related to CREB-BINDING PROTEIN and to E1A-ASSOCIATED P300 PROTEIN. They function as transcriptional coactivators by bridging between DNA-binding TRANSCRIPTION FACTORS and the basal transcription machinery. They also modify transcription factors and CHROMATIN through ACETYLATION.Hydroxamic Acids: A class of weak acids with the general formula R-CONHOH.Acetyl Coenzyme A: Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Sirtuins: A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.Lysine: An essential amino acid. It is often added to animal feed.N-Terminal Acetyltransferase E: An N-terminal acetyltransferase subtype that consists of the Naa50p catalytic subunit, and the Naa10p and Naa15p auxiliary subunits. It has specificity for the N-terminal METHIONINE of peptides where the next amino acid in the chain is hydrophobic.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Histone Deacetylase 1: A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 2; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.Histone Deacetylase 2: A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 1; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Methylation: Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Histone Code: The specific patterns of changes made to HISTONES, that are involved in assembly, maintenance, and alteration of chromatin structural states (such as EUCHROMATIN and HETEROCHROMATIN). The changes are made by various HISTONE MODIFICATION PROCESSES that include ACETYLATION; METHYLATION; PHOSPHORYLATION; and UBIQUITINATION.Histone Chaperones: Proteins involved in the assembly and disassembly of HISTONES into NUCLEOSOMES.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Histone Demethylases: Enzymes that catalyse the removal of methyl groups from LYSINE or ARGININE residues found on HISTONES. Many histone demethylases generally function through an oxidoreductive mechanism.Histone-Lysine N-Methyltransferase: An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC 2.1.1.43.Chromatin Assembly and Disassembly: The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Chromatin Immunoprecipitation: A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.CREB-Binding Protein: A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.E1A-Associated p300 Protein: A member of the p300-CBP transcription factors that was originally identified as a binding partner for ADENOVIRUS E1A PROTEINS.Butyrates: Derivatives of BUTYRIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxypropane structure.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Neoplasms, Cystic, Mucinous, and Serous: Neoplasms containing cyst-like formations or producing mucin or serum.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Jumonji Domain-Containing Histone Demethylases: A family of histone demethylases that share a conserved Jumonji C domain. The enzymes function via an iron-dependent dioxygenase mechanism that couples the conversion of 2-oxoglutarate to succinate to the hydroxylation of N-methyl groups.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Chromosomal Proteins, Non-Histone: Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Sirtuin 1: A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.Cell Line, Tumor: A cell line derived from cultured tumor cells.Protein Methyltransferases: Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.Heterochromatin: The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Skin Neoplasms: Tumors or cancer of the SKIN.Sirtuin 2: A sirtuin family member found primarily in the CYTOPLASM. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Neoplasms, Multiple Primary: Two or more abnormal growths of tissue occurring simultaneously and presumed to be of separate origin. The neoplasms may be histologically the same or different, and may be found in the same or different sites.Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Kidney Neoplasms: Tumors or cancers of the KIDNEY.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Neoplasms, Second Primary: Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause.DNA, Neoplasm: DNA present in neoplastic tissue.Gene Expression Regulation, Fungal: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.Anacardic Acids: A group of 6-alkyl SALICYLIC ACIDS that are found in ANACARDIUM and known for causing CONTACT DERMATITIS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Euchromatin: Chromosome regions that are loosely packaged and more accessible to RNA polymerases than HETEROCHROMATIN. These regions also stain differentially in CHROMOSOME BANDING preparations.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Lung Neoplasms: Tumors or cancer of the LUNG.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Thyroid Neoplasms: Tumors or cancer of the THYROID GLAND.Adenocarcinoma, Mucinous: An adenocarcinoma producing mucin in significant amounts. (From Dorland, 27th ed)

*RUNX1

These domains are necessary for RUNX1 to mediate DNA binding and protein-protein interactions respectively. The transcription ... This is further characterized histologically by the presence of Auer rods and epigenetically by lysine acetylation on residues ... Examples range from RUNX1 point mutations acquired from low-dose radiation leading to myelodysplastic neoplasms (MDN) or ... RUNX proteins form a heterodimeric complex with CBFβ which confers increased DNA binding and stability to the complex. ...

*Carcinogenesis

Known mechanisms of epigenetic change include DNA methylation, and methylation or acetylation of histone proteins bound to ... Oncogenes often produce mitogens, or are involved in transcription of DNA in protein synthesis, which creates the proteins and ... Mutant cells in neoplasms compete for space and resources. Thus, a clone with a mutation in a tumor suppressor gene or oncogene ... Epimutations can also occur by acetylation, methylation, phosphorylation or other alterations to histones, creating a histone ...

*Cancer epigenetics

However, since these HDAC inhibitors alter the acetylation state of many proteins in addition to the histone of interest, ... In certain types of cancer cells, the CTCF protein does not bind normally, and the p53 promoter accumulates repressive histone ... Such mutations and epigenetic alterations can give rise to cancer (see malignant neoplasms). Germ line mutations in DNA repair ... Other histone marks associated with tumorigenesis include increased deacetylation (decreased acetylation) of histones H3 and H4 ...

*N-alpha-acetyltransferase 10

... acetylation of ribosomal protein S18". Protein Science. 17 (10): 1781-90. doi:10.1110/ps.035899.108. PMC 2548364 . PMID ... "Expression of N-acetyl transferase human and human Arrest defective 1 proteins in thyroid neoplasms". Thyroid. 15 (10): 1131-6 ... "Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase ... Despite the fact that Nα-terminal acetylation of proteins has been known for many years, the functional consequences of this ...

*NAA15

Forte GM, Pool MR, Stirling CJ (May 2011). "N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum". ... "Expression of N-acetyl transferase human and human Arrest defective 1 proteins in thyroid neoplasms". Thyroid. 15 (10): 1131-6 ... "De novo mutations in histone-modifying genes in congenital heart disease". Nature. 498 (7453): 220-3. doi:10.1038/nature12141. ... Because TPR motifs mediate protein-protein interactions, it has been postulated that this domain may facilitate the interaction ...

*Proliferating cell nuclear antigen

Histone acetyltransferase • Histone deacetyltransferase • DNA methyltransferase • Sister-chromatid cohesion factors • Protein ... binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". J. ... or monoclonal antibody termed Ki-67 can be used for grading of different neoplasms, e.g. astrocytoma. They can be of diagnostic ... "Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300". Mol. Cell. 7 (6 ...

*Chromatin remodeling

... is that the histone modifications serve to recruit other proteins by specific recognition of the modified histone via protein ... Acetylation - by HAT (histone acetyl transferase); deacetylation - by HDAC (histone deacetylase) Acetylation tends to define ... several more subunits of the human SWI/SNF chromatin remodeling complex have been found mutated in a wide range of neoplasms. ... However, DNA is tightly packaged in the nucleus with the help of packaging proteins, chiefly histone proteins to form repeating ...

*Ubiquitin

... coordinating the cellular localization of proteins, activating and inactivating proteins, and modulating protein-protein ... Ubiquitin on histones also acts as a binding site for proteins that either activate or inhibit transcription and also can ... Kales SC, Ryan PE, Nau MM, Lipkowitz S (June 2010). "Cbl and human myeloid neoplasms: the Cbl oncogene comes of age". Cancer ... "DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics". Molecular and Cellular Biology. 27 ( ...

*Waldenström's macroglobulinemia

... "microRNA-dependent modulation of histone acetylation in Waldenström macroglobulinemia". Blood. 116 (9): 1506-1514. doi:10.1182/ ... Blood tests show the level of IgM in the blood and the presence of proteins, or tumor markers, that are the key symptoms of WM ... Serum protein electrophoresis results indicate evidence of a monoclonal spike but cannot establish the spike as IgM. An M ... ISBN 0-7817-5007-5. Frequency of lymphoid neoplasms. (Source: Modified from WHO Blue Book on Tumour of Hematopoietic and ...
The childhood heart disease of Friedreichs Ataxia (FRDA) is characterized by hypertrophy and failure. It is caused by loss of frataxin (FXN), a mitochondrial protein involved in energy homeostasis. FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity. Protein acetylation is an important regulator of cardiac metabolism and loss of SIRT3 increases susceptibility of the heart to stress-induced cardiac hypertrophy and ischemic injury. The underlying pathophysiology of heart failure in FRDA is unclear. The purpose of this study was to examine in detail the physiologic and acetylation changes of the heart that occur over time in a model of FRDA heart failure. We predicted that increased mitochondrial protein acetylation would be associated with a decrease in heart function in a model of FRDA ...
Because increased mitophagic flux enhances yeast mitochondrial fidelity (Kurihara et al., 2012) and more efficient mitochondrial function might ameliorate redox stress injury, we explored whether GCN5L1 KD cells are stress resilient. GCN5L1 depletion decreased rotenone-induced reactive oxygen species (ROS) generation, susceptibility to ionomycin-induced mitochondrial permeability transition, and enhanced resistance to paraquat-induced cell death (Fig. 4D-F).. To begin exploring this biology in vivo, GCN5L1-knockout (KO) mice were generated, but these were not viable. However, KO MEFs were harvested and showed the same mitochondrially restricted reduction in protein acetylation (supplementary material Fig. S5A,B) and mitochondrial enrichment of autophagy mediators (Fig. 4G; supplementary material Fig. S5C) as found in the KD studies. In addition, the reconstitution of GCN5L1 in these KO MEFs restored mitochondrial acetylation and reversed the mitochondrial ...
Serum and glucocorticoid-inducible kinase 1 (SGK1) is a serine/threonine kinase whose activity and expression is up-regulated in vascular neointimal lesions in association with restenosis. Our previous studies show that vascular smooth muscle cell (VSMC) proliferation is augmented upon activation of SGK1. However, the molecular mechanism(s) was not fully examined. Thus, to identify proteins that participate in SGK1-mediated stimulation of VSMC proliferation, we performed a kinase substrate protein array with activated SGK1. We identified sirtuin3 (Sirt3), a class III histone deacetylase as a novel putative substrate for SGK1 in this screen. Preliminary studies from two-dimensional SDS-PAGE indicate that expression of active SGK1 (S422D-SGK1) is associated with a shift in Sirt3 to a more acidic profile, consistent with an increase in phosphorylation. Moreover, S422D-SGK1 expression resulted in a 2- and 1.6-fold increase in Sirt3 mRNA and ...
Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in ...
The role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing of INF2 in epithelial RPE-1 cells produced a dramatic drop in tubulin acetylation, increased the G-actin/F-actin ratio, and impaired myocardin-related transcription factor (MRTF)/serum response factor (SRF)-dependent transcription, which is known to be repressed by increased levels of G-actin. The effect on tubulin acetylation was caused by the almost complete absence of α-tubulin acetyltransferase 1 (α-TAT1) messenger RNA (mRNA). Activation of the MRTF-SRF transcriptional complex restored α-TAT1 mRNA levels and tubulin acetylation. Several functional MRTF-SRF-responsive elements were consistently identified in the α-TAT1 gene. The effect of INF2 silencing on microtubule ...
Global alterations in histone acetylation levels have been observed in both normal and cancer cells and can be prognostic of clinical outcome. However, unlike site-specific acetylation changes that can affect transcription of particular genes, the reason for genome-wide changes has been less clear. Because acetyl-coA molecules required for histone acetylation and acetate anions generated by histone deacetylation are required for many metabolic processes, McBrian and colleagues hypothesized that metabolic or physiologic cues might affect global histone acetylation levels. Systematic testing of the effects of culture medium components on histone acetylation revealed that decreased sodium bicarbonate concentrations resulting in lowered extracellular and intracellular pH led to a rapid, marked reduction in total levels of ...
Protein acetylation affects gene expression, as well as other processes in cells, and it might be dependent on the availability of the metals. However, whether iron chelating compounds (siderophores) can have an effect on the acetylation process in plant roots is largely unknown. In the present study, western blotting and confocal microscopy was used to examine the degree of acetylation of histone H3 and alpha tubulin in Pinus sylvestris root cells in the presence of structurally different siderophores. The effect of metabolites that were produced by pathogenic and mycorrhizal fungi was also assessed. No effect was observed on histone acetylation. By contrast, the metabolites of the pathogenic fungus were able to decrease the level of microtubule acetylation, whereas treatment with iron-free ferrioxamine (DFO) was able to increase it. This latter was not observed when ...
Pathogen infection triggers complex molecular perturbations within host cells that results in either resistance or susceptibility. Protein acetylation is an emerging biochemical modification that appears to play central roles during host-pathogen interactions. To date, research in this area has focused on two main themes linking protein acetylation to plant immune signaling. Firstly, it has been established that proper gene expression during defense responses requires modulation of histone acetylation within target gene promoter regions. Second, some pathogens can deliver effector molecules that encode acetyltransferases directly within the host cell to modify acetylation of specific host proteins. Collectively these findings suggest that the acetylation level for a range of host proteins may be modulated to alter the outcome of pathogen ...
Sirt3 is a mitochondrial NAD+-dependent deacetylase that governs mitochondrial metabolism and reactive oxygen species homeostasis. Sirt3 deficiency has been reported to accelerate the development of the metabolic syndrome. However, the role of Sirt3 in atherosclerosis remains enigmatic. We aimed to investigate whether Sirt3 deficiency affects atherosclerosis, plaque vulnerability, and metabolic homeostasis. Low-density lipoprotein receptor knockout (LDLR −/−) and LDLR/Sirt3 double-knockout (Sirt3 −/− LDLR −/−) mice were fed a high-cholesterol diet (1.25 % w/w) for 12 weeks. Atherosclerosis was assessed en face in thoraco-abdominal aortae and in cross sections of aortic roots. Sirt3 deletion led to hepatic mitochondrial protein hyperacetylation. Unexpectedly, though plasma malondialdehyde levels were elevated in Sirt3-deficient mice, Sirt3 deletion affected neither plaque burden nor features of plaque vulnerability (i.e., fibrous cap thickness and necrotic ...
In this study, we analyzed the equilibrium between histone acetylation, mediated by HATs, and histone deacetylation, mediated by HDACs, in the NAWM of chronic MS brains. Similar to what was reported for the old rodent brain, also in the NAWM of human brains from aged individuals and chronic MS patients we detected a shift toward acetylation. This shift toward acetylation detected in a subset of female patients correlated with the consistent and reproducible increase of several histone acetyltransferase family members, including CBP, P300, MYST3, and MYST4. It is worth noting that, although we also detected increased levels of HDAC11 in this subpopulation, the increased of the acetyltransferases was much greater and likely determined the shift in favor of increased acetylation. These differences were most prominent in a subset of female MS patients and were associated with ...
Posttranslational modification of proteins by acetylation and phosphorylation regulates most cellular processes in living organisms. Surprisingly, the evolutionary conservation of phosphorylated serine and threonine residues is only marginally higher than that of unmodified serines and threonines. With high-resolution mass spectrometry, we identified 1981 lysine acetylation sites in the proteome of Drosophila melanogaster. We used data sets of experimentally identified acetylation and phosphorylation sites in Drosophila and humans to analyze the evolutionary conservation of these modification sites between flies and humans. Site-level conservation analysis revealed that acetylation sites are highly conserved, significantly more so than phosphorylation sites. Furthermore, comparison of lysine conservation in Drosophila and humans with that in nematodes and zebrafish revealed that acetylated lysines were significantly more ...
The process of histone acetylation at lysine residues by histone acetyltransferase (HAT) is an important epigenetic marker and can be measured with the use of histone lysine acetylation antibodies . Acetylation of histones...
In lower organisms such as yeast, silent information regulator 2 (Sir2), a NAD-dependent deacetylase, links the metabolic activity of yeast to its aging phenotype. Mammals have seven Sir2 homologs, SIRT1-7, which have conserved NAD-dependent deacetylase and/or ADP-ribosyltransferase activities. Although mammalian sirtuins have not been shown to regulate life span, they affect various cellular proc... read moreesses including cell survival and metabolism. In this project, we study SIRT5, a mitochondrial sirtuin previously shown to regulate carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme of the urea cycle, via reversible acetylation. Our aim was to determine whether SIRT5 regulates cholesterol metabolism. We show that SIRT5 KO mice on high cholesterol diet had lower levels of cholesterol and triglycerides in their serum, but this phenotype did not repeat in a following trial. Also, we show that expression levels of select genes in mitochondrial oxidative phosphorylation are ...
Enoyl-coenzyme A hydratase/3-hydroxyacyl-coenzyme A (EHHADH) is an important enzyme which catalyze two steps in fatty acid oxidation. There are four acetylated lysine residues been identified in EHHADH, which are Lys165, Lys171, Lys346 and Lys584. Immunoprecipitation of ectopically expressed FLAG-tagged EHHADH and Western blotting with antibody to acetyllysine confirmed that EHHADH was indeed acetylated(Zhao, et al). In order to explore the effect of acetylation on fatty acid oxidation. Isobaric tags are used, which is TSA and NAM. TSA and NAM treatment increased all the four lysine residues acetylation. Consistently, corresponding unacetylated peptide was decreased. Scientists treat TSA and NAM to Chang Human Liver cells doubled the activity of EHHADH, which indicates that acetylation of EHHADH would increase fatty acid oxidation pathway. In order to confirm the result, site-directed mutagenesis was used and the four lysine residue was replaced by ...
The distribution of acetylated isoforms of histone H4 along Chinese hamster chromosomes has been studied by immunostaining with antibodies recognizing H4 acetylated at defined lysines in its N-terminal domain. The heterochromatic long arm of the X chromosome in both female (CHO) and male (DON) cell lines is underacetylated at three out of four lysines (5, 8, and 12). In contrast, the level of acetylation at lysine 16, which is the first to be acetylated in mammals, was similar in X chromosomes and autosomes. Labeling of the cells with bromodeoxyuridine (BrdU) to mark late-replicating chromosome domains, followed by double immunostaining with antibodies to BrdU and acetylated H4, showed a close, though not perfect, correlation between late replication and low levels of H4 acetylation. The results show that levels of histone acetylation are associated with the replication timing of defined domains on both the X chromosome and ...
Many studies have shown that SIRT3 deficiency results in increased mitochondrial acetylation and reduced activity of numerous mitochondrial enzymes (Newman et al, 2012). SIRT3 protein levels are increased upon fasting and calorie restriction (Shi et al, 2005; Palacios et al, 2009; Hirschey et al, 2010; Tao et al, 2010; Newman et al, 2012), and increased SIRT3 activity has been suggested to regulate metabolism under these conditions. However, with the exception of a single study (Fan et al, 2014), a regulatory axis between enzyme‐catalyzed acetylation and SIRT3‐mediated deacetylation has not been demonstrated. A hallmark of protein regulation by posttranslational modifications is site‐specific, enzyme‐catalyzed modification that mostly occurs in a conditional manner. However, there is little evidence of enzyme‐catalyzed, site‐specific acetylation in mitochondria, and several studies suggest that most ...
Long-lasting memories require specific gene expression programmes that are, in part, orchestrated by epigenetic mechanisms. Of the epigenetic modifications identified in cognitive processes, histone acetylation has spurred considerable interest. Whereas increments in histone acetylation have consistently been shown to favour learning and memory, a lack thereof has been causally implicated in cognitive impairments in neurodevelopmental disorders, neurodegeneration and ageing. As histone acetylation and cognitive functions can be pharmacologically restored by histone deacetylase inhibitors, this epigenetic modification might constitute a molecular memory aid on the chromatin and, by extension, a new template for therapeutic interventions against cognitive frailty.. Read more → ...
Histone acetylation is a hallmark of chromatin that has an open structure that can be accessed by DNA and RNA polymerases as well as transcription factors, resulting in the activation of gene transcription (Filippakopoulos and Knapp, 2014). Correspondingly, histone methylation increases the basicity and hydrophobicity of histone tails and the affinity of certain proteins, such as transcription factors, toward DNA (Teperino et al., 2010), thus affecting the gene expression. In this database, we have collected 584 non-redundant protein data of 8 organisms including H. sapiens, M. musculus, R. norvegicus, D. melanogaster, C. elegans, A. thaliana, S. pombe and S. cerevisiae from the literature. The data are further classified into 15 families for histone acetylation writers, erasers and readers and 32 families for histone methylation writers, erasers and ...
This study shows that Rb is a key regulator of differentiation and that acetylation is an important modification during this process. We have investigated the role of Rb acetylation in keratinocyte differentiation by mutating the major acetylation sites, lysines 873 and 874, to arginine and then determining the ability of the mutant to restore differentiation in Rb-knockdown keratinocytes. Mutation of the acetylation sites did not affect the ability of Rb to inhibit the proliferation, probably because of the fact that RbRR can interact with and inhibit E2F1 (Markham et al., 2006). This also suggests that inhibition of E2F family members is not sufficient to induce terminal differentiation, as has previously reported in the Saos-2 cell line (Sellers et al., 1998). However, unlike wild-type Rb, the acetylation mutant is unable to induce either early or late differentiation markers and, because Rb is acetylated relatively late ...
The well‐known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS‐1/TRR‐1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans. Our results show that these beneficial effects are largely mediated through transcriptional up‐regulation of the FOXO transcription factor DAF‐16. MYS‐1 and TRR‐1 are recruited to the promoter regions of the daf‐16 gene, where they play a role in histone acetylation, including H4K16 acetylation. Remarkably, we also find that the human MYST family Tip60/TRRAP complex promotes ...
The well‐known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS‐1/TRR‐1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans. Our results show that these beneficial effects are largely mediated through transcriptional up‐regulation of the FOXO transcription factor DAF‐16. MYS‐1 and TRR‐1 are recruited to the promoter regions of the daf‐16 gene, where they play a role in histone acetylation, including H4K16 acetylation. Remarkably, we also find that the human MYST family Tip60/TRRAP complex promotes ...
In chromosome translocations characteristic of Burkitt lymphomas (BL) and murine plasmacytomas, c-myc genes become juxtaposed to immunoglobulin heavy-chain (IgH) sequences, resulting in aberrant c-myc transcription. Translocated c-myc alleles that retain the first exon exhibit increased transcription from the normally minor c-myc promoter, P1, and increased transcriptional elongation through inherent pause sites proximal to the major c-myc promoter, P2, We recently demonstrated that a cassette derived from four DNase I-hypersensitive sites (HS1234) in the 3C alpha region of the IgH locus functions as an enhancer-locus control region (LCR) and directs a similar pattern of deregulated expression of linked c-myc genes in BL and plasmacytoma cell lines. Here, we report that the HS1234 enhancer-LCR mediates a widespread increase in histone acetylation along linked c-myc genes in Raji BL cells. Significantly, the increase in acetylation was not restricted to ...
Transcription in eukaryotes occurs in the context of DNA packaged into chromatin. The basic unit of chromatin is the nucleosome, in which DNA is wrapped around the core histones H2A, H2B, H3, and H4. Nucleosome remodeling complexes such as Swi-Snf can facilitate opening of repressive chromatin structures in promoter regions to provide access for DNA-binding activator proteins or general transcription factors (32). In addition, reversible chromatin modifications such as acetylation, phosphorylation, and methylation of N-terminal histone tails can modulate accessibility of DNA within chromatin (56). Acetylation of lysines in the histone tails neutralizes their positive charge, thereby weakening electrostatic interactions with DNA (25) and interactions between neighboring nucleosomes (42). The tails of histones H3 and H4 are important for transcriptional regulation of numerous genes, because ...
Aspergillus oryzae is ubiquitous filamentous fungi in nature and has been used in a number of industries such as Japanese traditional fermented foods and pharmaceutical products. In nature and industries, A. oryzae adapt to various environmental conditions by global change of transcriptional regulation. In the previous study, we revealed that the expression of histone acetylation related genes were affected by the growth phase and alteration of growing environment, such as culture conditions and stress exposing. In general, histone acetylation plays the fundamental roles for the genes expression, and closely relates to growth, morphology, differentiation and stress responses. Recently, several reports indicate that histone acetylation also plays important roles in filamentous fungi. In this context, we focused on histone acetylation related genes, particularly ...
Both isoforms of the hepatitis delta antigen (HDAg) of hepatitis delta virus (HDV) are highly associated with virus proliferation and may act as co-activators of cellular gene expression. Human hepatocellular carcinoma (HCC) cell line Huh7, which stably expresses HDAgs, was differentially screened and the results showed that clusterin gene expression was enhanced. The mechanisms for HDAg-mediated clusterin gene upregulation were investigated. Expression of HDAgs was associated with enhanced histone H3 acetylation within the clusterin promoter in a chromatin immunoprecipitation assay. Transient transfection of HDAg-expressing plasmids into Huh7 cells also enhanced clusterin expression and histone acetylation. Furthermore, HDV replication was associated with histone hyperacetylation and clusterin induction. The effect of increased clusterin expression was determined by a chemosensitivity assay with adriamycin ...
Author: Henriksen, Peter et al.; Genre: Journal Article; Published in Print: 2012-11; Open Access; Keywords: SISTER-CHROMATID COHESION; MASS-SPECTROMETRY; HISTONE ACETYLATION;|br/| SIGNALING NETWORKS; ESCHERICHIA-COLI; C-TRAP; YEAST; COMPLEXES;|br/| DEACETYLATION; PHOSPHORYLATION; Title: Proteome-wide Analysis of Lysine Acetylation Suggests its Broad|br/| Regulatory Scope in Saccharomyces cerevisiae
Proteins lysine deacetylases (KDACs), like the vintage Zn2+-reliant histone deacetylases (HDACs) as well as the nicotinamide adenine dinucleotide (NAD+)-requiring sirtuins, are enzymes that play critical functions in various biological processes, specially the epigenetic rules of global gene manifestation applications in response to internal and exterior cues. manipulation of endogenous signaling pathways. With this Minireview, we discuss our present understanding of the mobile settings of KDAC activity and types of their pharmacologic rules. strong course="kwd-title" Keywords: epigenetics, histone deacetylases (HDACs), homeostasis, lysine deacetylases (KDACs), multiprotein complexes, pharmacologic rules, sirtuins Introduction Proteins lysine acetylation, including enzymatic transfer of the acetyl group from your cofactor acetyl coenzyme A (acetyl-CoA) towards the terminal amine present on lysine part ...
ERRα interacts with the mouse Sirt3 promoter in vitro and in vivo.A, Electrophoretic mobility shift assay was executed using a biotin probe. Biotin-labeled dou
The accessibility of regulatory elements in chromatin represents a principal rate-limiting parameter of gene transcription and is modulated by enzymatic transcriptional co-factors that alter the topology of chromatin or covalently modify histones (e.g. by acetylation). The bone-specific activation and 1,25-dihydroxyvitamin D(3) enhancement of osteocalcin (OC) gene transcription are both functionally linked to modifications in nucleosomal organization. The initiation of tissue-specific basal transcription is accompanied by the induction of two DNase I hypersensitive sites, and this chromatin remodeling event requires binding of the key osteogenic factor RUNX2/CBFA1 to the OC promoter. Here, we analyzed the acetylation status of histones H3 and H4 when the OC gene is active (in osteoblastic ROS17/2.8 cells) or inactive (in fibroblastic ROS24/1 cells) using chromatin immunoprecipitation assays. We find that acetylated histone ...
In eukaryotic cells DNA is associated with histones and other proteins to form chromatin. The basic unit of chromatin is the nucleosome consisting of 140 bp of DNA wrapped around an octameric core of the four conserved histones H2A, H2B, H3 and H4.

The relatively unstructured and highly charged N-terminal tail domains of histones, are central to the processes that modulate chromatin structure. A diverse and elaborate array of post-translational modifications that include acetylation, phosphorylation, methylation, ubiquitination and ADP-ribosylation, occur on the N-terminal tail domains of histones. Acetylation of lysine residues within these N-terminal domains by histone acetyl-transferases (HATs), is associated with transcriptional activation. This modification results in remodeling of the nucleosome structure into an open conformation more accessible to ...
Sirtuin 6, an NAD+-dependent deacetylase and mono-ADP-ribosyl transferase, is known to have an anti-inflammatory function. It is unclear, however, whether sirtuin 6 also negatively contributes to the development of allergic airway inflammation (AAI). To elucidate the role of sirtuin 6 in AAI pathogenesis and its underlying mechanism. An adenovirus expressing Sirt6 (AdSirt6) and a catalytically inactive Sirt6-H133Y were used to deliver sirtuin 6. We analyzed the features of AAI in BALB/c mice after sensitization with two different allergens, ovalbumin (OVA) and house dust mite (HDM). Sirtuin 6 level increased in lung tissues of OVA-challenged mice. AdSirt6 injection before allergen challenge reduced all cardinal features of AAI; eosinophilic airway inflammation, mucus hypersecretion, airway hyperresponsiveness, and Th2 immune responses were markedly suppressed. Furthermore, the differentiation of CD4+ T cells into Th2 cells was also decreased in the draining lymph nodes of AdSirt6-injected mice. ...
ObjectiveTo examine the ability of a broad-spectrum histone deacetylase (HDAC) inhibitor to protect cartilage in vivo, and to explore the effects of class-selective HDAC inhibitors and small interfering RNA (siRNA)-induced knockdown of HDACs on metalloproteinase expression and cartilage degradation in vitro. MethodsA destabilization of the medial meniscus (DMM) model was used to assess the in vivo activity of the HDAC inhibitor trichostatin A (TSA). Human articular chondrocytes (HACs) and SW-1353 chondrosarcoma cells were treated with cytokines and TSA, valproic acid, MS-275, or siRNA, and quantitative reverse transcription-polymerase chain reaction was performed to determine the effect of treatment on metalloproteinase expression. HDAC inhibitor activity was detected by Western blotting. A bovine nasal cartilage (BNC) explant assay was performed to measure cartilage resorption in vitro. ResultsSystemically administered TSA protected cartilage in the DMM ...
Thyroid cancer has been indicated to have a higher global proportion of DNA methylation and a decreased level of histone acetylation. Previous studies showed that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. The goal of this research was to study the endoplasmic reticulum (ER) stress-mediated actions of the dominant histone deacetylase (HDAC) inhibitor, N-hydroxy-7-(2-naphthylthio) hepatonomide (HNHA), in thyroid cancer and to explore its effects on apoptotic cell death pathways. Experiments were achieved to conclude the effects of HNHA in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) cell lines and xenografts, as compared with two other established HDAC inhibitors (SAHA; suberoylanilide hydroxamic acid and TSA; trichostatin A). Apoptosis, which was induced by all HDAC inhibitors, was particularly significant in HNHA-treated cells, where ...
Specifically acetylates Lys-40 in alpha-tubulin on the lumenal side of microtubules. Promotes microtubule destabilization and accelerates microtubule dynamics; this activity may be independent of acetylation activity. Acetylates alpha-tubulin with a slow enzymatic rate, due to a catalytic site that is not optimized for acetyl transfer. Enters the microtubule through each end and diffuses quickly throughout the lumen of microtubules. Acetylates only long/old microtubules because of its slow acetylation rate since it does not have time to act on dynamically unstable microtubules before the enzyme is released. Required for normal sperm flagellar function. Promotes directional cell locomotion and chemotaxis, through AP2A2-dependent acetylation of alpha-tubulin at clathrin-coated pits that are concentrated at the leading edge of migrating cells. May facilitate primary cilium assembly ...
Title: Chemical Origins of Isoform Selectivity in Histone Deacetylase Inhibitors. VOLUME: 14 ISSUE: 6. Author(s):Alan P. Kozikowski and Kyle V. Butler. Affiliation:University of Illinois at Chicago, Department of Medicinal Chemistry, 833 S. Wood St., Chicago, Illinois 60612, USA.. Keywords:Histone deacetylase inhibitor, HDAC, isoform selective, epigenetics. Abstract: Histones undergo extensive posttranslational modifications that affect gene expression. Acetylation is a key histone modification that is primarily regulated by two enzymes, one of which is histone deacetylase (HDAC). The activity of HDAC causes transcriptional silencing of DNA. Eleven distinct zinc-dependent histone deacetylase isoforms have been identified in humans. Each isoform has a unique structure and function, and regulates a unique set of genes. HDAC is responsible for the regulation of many genes involved in cancer ...
Title: The Role of NAD+ Dependent Histone Deacetylases (sirtuins) in Ageing. VOLUME: 7 ISSUE: 11. Author(s):Johannes Trapp. Keywords:protein deacetylation, transesterification, Resveratrol, sirtuin inhibitor, Splitomicin. Abstract: Histone deacetylases (HDACs) are enzymes that are able to deacetylate lysine side chains in histones and certain non-histone proteins which leads to altered states of conformation and activity for the proteins in question. Three classes of histone deacetylases have been recognized in humans. Class I and II are zinc-dependent amidohydrolases and eleven subtypes have been discovered (HDAC1-11). Class III enzymes depend in their catalysis on NAD+ and subsequently, O-acetyl ADP ribose and nicotinamide are formed as a consequence of the acetyl transfer. Due to the homology to the yeast histone deacetylase Sir2p the ...
This integrations article considers data from Kotak et al. 2019 and Trachtman et al. 2019. Our interest is in understanding the place of chromatin modifiers in developmental control pathways, working in concert with or in parallel to established transcriptional factor networks, hormonal signaling, etc.. Previously we have described how the histone acetyltransferase GCN5 and its associated transcriptional coactivator ADA2b affect trichome morphogenesis (Kotak et al. 2018). We have now shown that these epigenetic factors also play a role in specification of trichome cell fate, as evidenced by an increase in trichome number and/or density in disruption mutant backgrounds (Kotak et al. 2019). Wang et al. 2019 also recently showed an increase in trichome density on the first pair of true leaves in several gcn5 mutant backgrounds. Therefore, GCN5 and ADA2b act to limit trichome initiation (Fig. 1) from a field of epidermal leaf cells, a well-described developmental process involving many genes ...
Histone acetylation is one of the vital reversible modifications of chromatin structure that regulates gene expression in eukaryotes. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) maintain the homeostasis of histone acetylation. Studies in Arabidopsis have revealed that HATs are involved in plant responses to various stresses including light, temperature, salt and ABA. Drought stress, a very common environmental stress, could cause a range of physiological and biochemical responses in plants involving HATs. Eight HATs in four different families (CBP, GNAT, MYST, and TAFII250 family) are known in rice. In this research, four OsHATs, one from each family, were chosen based on in silico domain and promoter analysis for their response under drought conditions. Drought stress was introduced to two-leaf-stage rice seedlings. The effectiveness of drought treatment was confirmed by the ...
Acetic anhydride is an esterification agent for use in prepn. of modified food starch and for acetylation of monoglycerides Acetic anhydride is a versatile reagent for acetylations, the introduction of acetyl groups to organic substrates. In these conversions, acetic anhydride is viewed as a source of CH3CO+. Alcohols and amines are readily acetylated. For example, the reaction of acetic anhydride with ethanol yields ethyl acetate: (CH3CO)2O + CH3CH2OH → CH3CO2CH2CH3 + CH3COOH. Acetic anhydride is an irritant and flammable. Because of its reactivity toward water, alcohol foam or carbon dioxide are preferred for fire suppression. The vapour of acetic anhydride is harmful. Acetic anhydride is the chemical compound with the formula (CH3CO)2O. Commonly abbreviated Ac2O, it is one of the simplest acid anhydrides and is a widely used reagent in organic synthesis. It is a colorless liquid that smells strongly of acetic acid, which is formed by its reaction with the moisture in the ...
Benhamed, Moussa, Martin-Magniette, Marie-Laure, Taconnat, Ludivine, Bitton, Frederique, Servet, Caroline, De Clercq, Rebecca, De Meyer, Bjorn, Buysschaert, Caroline, Rombauts, Stephane, Villarroel, Raimundo, Aubourg, Sebastien, Beynon, Jim, Bhalerao, Rishikesh P., Coupland, George, Gruissem, Wilhelm, Menke, Frank L. H., Weisshaar, Bernd, Renou, Jean-Pierre, Zhou, Dao-Xiu, and Hilson, Pierre. "Genome-scale Arabidopsis promoter array identifies targets of the histone acetyltransferase GCN5". The Plant Journal 56.3 (2008): 493-504 ...
[152 Pages Report] Check for Discount on Global Histone Deacetylase Inhibitors Industry 2016 Market Research Report report by QYResearch Group. The Global Histone Deacetylase Inhibitors Industry 2016 Market Research Report...
In vivo tracking of histone H3 lysine 9 acetylation in Xenopus laevis during tail regenerationIn vivo tracking of histone H3 lysine 9 acetylation in Xenopus laevis during tail regeneration ...
Background: Reversible lysine-acetylation of proteins is regulated by histone acetyl transferases and deacetylases (HDACs). Previous studies from this laboratory have shown that a class-II HDAC, HDAC4 is associated with cardiac sarcomeres, and that HDAC-inhibitors enhance the contractile activity of myofilaments. Since, HDAC4 has little or no deacetylase activity of its own, this study was undertaken to examine the presence of other HDACs on cardiac sarcomeres.. Methods and Results: We prepared skinned papillary muscle fibers of the mouse heart and subjected them to western analysis. Results showed that a class-I HDAC, HDAC3 was localized to cardiac sarcomeres. By immuno-histochemical and electron microscopic analyses we found that HDAC3 was localized to the A-band of cardiac sarcomeres. We therefore examined the reversible acetylation of the A-band protein, myosin heavy chains (MHCs). MHC isoforms were prepared from control ...
The essential histone H3 variant Cse4 plays a crucial role at the centromere in S. cerevisiae, where it replaces histone H3 in that it assembles centromere specific (Cse4-H4)2 tetrameres. We found in our study that the histone H3 variant was able to interact over its unique N-Terminus with two subunits of the histone acetyltransferase complex SAS-I: Sas2 and Sas4. Mutations within the acetyl-CoA binding site (HAT domain) or the zink-finger of Sas2 disrupted the binding to Cse4, although an indirect interaction was found with co-immunoprecipitation experiments. Additionally, the N-terminus of Cse4 interacted with Cac1, the largest subunit of the chromatin assembly factor CAF-I and Asf1 - two histone chaperones that assemble histones H3 and H4 into nucleosomes. Our findings further suggest a role of Cac1 independent of Cac2 and Cac3 as no binding to Cse4 could be detected. A role for Sas2 at the centromere was ...
The influence of acetylation status of tuberculosis patients on the isoniazid serum concentrations and sputum conversion after intensive phase therapy
The genome is organised into large scale structures in the interphase nucleus. Pericentromeric heterochromatin represents one such compartment characterised by histones H3 and H4 tri-methylated at K9 and K20 respectively and with a correspondingly low level of histone acetylation. HP1 proteins are concentrated in pericentric heterochromatin and histone deacetylase inhibitors such as trichostatin A (TSA) promote hyperacetylation of heterochromatic nucleosomes and the dispersal of HP1 proteins. We observed that in mouse cells, which contain prominent heterochromatin, DNA topoisomerase IIb (topoIIb) is also concentrated in heterochromatic regions. Similarly, a detergent-resistant fraction of topoIIb is associated with heterochromatin in human cell lines. Treatment with TSA displaced topoIIb from the heterochromatin with similar kinetics to the displacement of HP1b. Topoisomerase II is the ...
In order to explore this, the histone deacetylase inhibitor valproic acid (VPA) was used to induce hyperacetylation of histones in embryonic stem cells. Surprisingly, although global levels of acetyl marks were highly increased by VPA treatment (up to 16-fold), only 10% of genes showed transcriptional changes. Interestingly, these global changes in histone modification were not reflected in the changes at individual genes where increases in acetylation were rarely greater than 2-fold. Furthermore, changes in acetylation levels did not correlate with transcriptional effects. Wash-out experiments showed that transient VPA treatment could not induce long term effects on transcription, even during ES cell differentiation when histone modifications play a crucial role. Finally, the role of polycomb silencing in the response to VPA treatment was assessed using an ES cell line in which the polycomb ...
In this reaction, the hydrogen atom that belongs to cellulose hydroxyl is replaced by an acetic group from acetic anhydride, yielding a carboxylic acid and an ester group in the wood, which is less polar to strong hydroxyl. This strategy renders wood more compatible with apolar polymers such as polyolefins.. Hence, the objectives of this study were to verify the effects of the proportion of acetic acid/anhydride on the acetylation of wood flour at varying times and temperatures and to examine hydroxyl and carbonyl groups by FTIR. The influence of these parameters was verified by experiments with a factorial design and partial least squares regression, both useful techniques for obtaining information concerning the effect of parameters in a given process.25-28 EXPERIMENTAL. Materials. Wood flour (100 mesh) from Pinus sp. trees, with a density of 0.25 g/cm³, was supplied by Pinhopó Ltda. Acetic acid and acetic anhydride (both from Biotec) were used in different ratios in the ...
Aminoglutethimide (AG) 500 mg was administered orally to four normal volunteers and eight patients undergoing treatment for metastatic breast cancer. In each subject the acetylator phenotype was established from the monoacetyldapsone (MADDS)/dapsone (DDS) ratio. Acetylaminoglutethimide (acetylAG) rapidly appeared in the plasma and its disposition paralleled that of AG. A close relationship (P less than 0.01) was observed between the acetyl AG/AG and MADDS/DDS ratio suggesting that AG may undergo polymorphic acetylation like DDS. AG half-life was 19.5 +/- 7.7 h in seven fast acetylators of DDS and 12.6 +/- 2.3 h in five slow acetylators and its apparent metabolic clearance was significantly (P less than 0.01) related to the acetylAG/AG ratio. Over 48 h the fast acetylators excreted 7.7 +/- 4.4% of the administered AG dose in the urine as unchanged AG as compared to 12.4 +/- 2.8% in slow acetylators. A much smaller fraction of the dose was excreted as acetylAG: 3.6 +/- 1.5% by fast and 1.9 +/- ...
TY - JOUR. T1 - NAT2 fast acetylator genotype is associated with an increased risk of colorectal cancer in Taiwan. AU - Huang, Chi Chou. AU - Chien, Wen Pin. AU - Wong, Ruey Hong. AU - Cheng, Ya Wen. AU - Chen, Meng Cheng. AU - Chou, Ming Chih. AU - Lee, Huei. PY - 2007/7. Y1 - 2007/7. N2 - In Taiwan, colorectal cancer has one of the highest rates of increased incidence in the past two decades. Heterocyclic amines from dietary cooked meats are metabolically activated by NAT2 (N-acetyltransferase 2), which are associated with colorectal cancer incidence. Thus, the NAT2 fast acetylator genotype may be associated with colorectal cancer risk. However, the association between the NAT2 genotype and colorectal cancer risk is not clearly understood. We conducted a study with 244 primary colorectal cancer cases and 299 cancer-free healthy control subjects to verify the association of NAT2 polymorphisms with the risk of Taiwanese colorectal cancer. Our data showed that subjects with the NAT2 W/W ...
Hormonal therapy resistance remains a considerable barrier in the treatment of breast cancer. Activation of the Akt-PI3K-mTOR pathway plays an important role in hormonal therapy resistance. Our recent preclinical and clinical studies showed that the addition of a histone deacetylase inhibitor re-sensitized hormonal therapy resistant breast cancer to tamoxifen. As histone deacetylases are key regulators of Akt, we evaluated the effect of combined treatment with the histone deacetylase inhibitor PCI-24781 and tamoxifen on Akt in breast cancer cells. We demonstrate that while both histone deacetylase and estrogen receptor inhibition down regulate AKT mRNA and protein, their concerted effort results in down regulation of AKT activity with induction of cell death. Histone deacetylase inhibition exerts its effect on AKT mRNA through an estrogen receptor-dependent mechanism, primarily down regulating the most ...
Histone acetylation plays an essential role in many DNA-related processes such as transcriptional regulation via modulation of chromatin structure. Many histone acetytransferases have been discovered and studied in the past few years, but the roles of different histone acetyltransferases (HAT) during mammalian development are not well defined at present. Gcn5 histone acetyltransferase is highly expressed until E16.5 during development. Previous studies in our lab using a constitutive null allele demonstrated that Gcn5 knock out mice are embryonic lethal, precluding the study of Gcn5 functions at later developmental stages. The creation of a conditional Gcn5 null allele, Gcn5flox allele, bypasses the early lethality. Mice homozygous for this allele are viable and appear healthy. In contrast, mice homozygous for a Gcn5 Δex3-18 allele created by Cre-loxP mediated deletion display a phenotype identical to our original Gcn5 null ...
Full Text - Inducing cardiomyocyte proliferation is a hopeful approach for cardiac regeneration following myocardial infarction. Previous studies have shown that p21 inhibits the cardiomyocyte proliferation and cardiac regeneration. Deacetylation of p21 by Sirt1 deacetylase may reduce p21 abundance and remove p21-induced cell cycle arrest. However, whether p21 deacetylation and Sirt1 deacetylate control cardiomyocyte proliferation is unclear. Here, we show that acetylation of p21 induces cardiomyocyte proliferation arrest, whereas blocking the acetylation of p21 increases cardiomyocyte proliferation. P21 can be acetylated by Sirt1, and Sirt1 activate p21 ubiquitination through deacetylation. Additionally, overexpression of Sirt1 induces EdU-, pH3-, and Aurora B-positive cardiomyocytes in neonatal and adult mice. In contrast, depletion of Sirt1 reduces cardiomyocyte proliferation in vitro and in vivo. Moreover, ...
Acetyl coenzyme A-dependent N-acetyltransferase and O-acetyltransferase activities were examined in liver cytosols derived from homozygous rapid acetylator C57BL/6J and A.B6 congenic inbred mouse strains, from homozygous slow acetylator A/J and B6.A congenic inbred mouse strains, and from the (C57BL/6J x A/J)F1 heterozygous acetylator hybrid mouse strain. Acetylator genotype-dependent N-acetyltransferase activity was exhibited for the N-acetylation of p-aminobenzoic acid, 2-aminofluorene, and 4-aminobiphenyl. In contrast, levels of isoniazid N-acetyltransferase and N-hydroxy-3,2-dimethyl-4-aminobiphenyl O-acetyltransferase activities in mouse liver cytosol appeared to be independent of the arylamine Nat acetylator gene. Although cytosolic N-acetyltransferase activities differed about 2-fold between the parental C57BL/6J and A/J strains for p-aminobenzoic acid, 2-aminofluorene, and 4-aminobiphenyl, the same N-acetyltransferase activities differed about 6-7-fold between the homozygous rapid ...
Black tar heroin is a free base form of heroin that is sticky like tar or hard like coal. Its dark color is the result of crude processing methods that leave behind impurities. Despite its name, black tar heroin can also be dark orange or dark brown in appearance. It is generally less expensive than other forms of heroin.[1] Black tar heroin is impure morphine diacetate. Other forms of heroin require additional steps of purification post acetylation. With black tar the products processing stops immediately after acetylation. Its unique consistency however is due to acetylation without a reflux apparatus. As in homebake heroin in Australia and New Zealand the crude acetylation results in a gooey mass. Black Tar as a type holds a variable admixture morphine derivatives-predominantly 6-MAM (6-monoacetylmorphine) which is another result of crude acetylation. The lack of proper reflux during acetylation fails to ...
HTF Market Intelligence released a new research report of 46 pages on title NAD Dependent Protein Deacetylase Sirtuin 1 (SIR2 Like Protein 1 or Sirtuin Type 1 or Regulatory Protein SIR2 Homolog 1 or SIRT1 or EC 3.5.1.) - Pipeline Review, H1 2017 with detailed analysis, forecast and strategies. The study covers key regions and important players such as GlaxoSmithKline Plc, Jyant Technologies Inc
3) Isoniazid Easy question would be..Which drugs dont cause SLE. Yes. Because they are related to acetylators. The slow and fast acetylators. Can you explain I mean how does it effect? The slow and fast acetylators?. Im not sure.. But the slow acetylators are more prone to DILE. Ill cross check and let you know. Slow acetylators metabolize the drug slowly.. Hence a higher chance of toxicity. Presumably, this is because acetylation of the aromatic amine or hydrazine functional group leads to a non-toxic product. Several other drugs which have been implicated in drug-induced lupus also contain an aromatic amine or hydrazine group. The clinical and laboratory characteristics of drug-induced and idiopathic lupus are similar but the degree to which the pathophysiological mechanisms are related, if at all, is unknown ...
Histone deacetylases are important targets for cancer therapeutics, but their regulation is poorly understood. Our data show coordinated transcription of HDAC1 and HDAC2 in lung cancer cell lines, but suggest HDAC2 protein expression is cell-context specific. Through an unbiased siRNA screen we found that BRCA1-associated protein 1 (BAP1) regulates their expression, with HDAC2 reduced and HDAC1 increased in BAP1 depleted cells. BAP1 loss-of-function is increasingly reported in cancers including thoracic malignancies, with frequent mutation in malignant pleural mesothelioma. Endogenous HDAC2 directly correlates with BAP1 across a panel of lung cancer cell lines, and is downregulated in mesothelioma cell lines with genetic BAP1 inactivation. We find that BAP1 regulates HDAC2 by increasing transcript abundance, rather than opposing its ubiquitylation. Importantly, although total cellular HDAC activity is unaffected by transient depletion of HDAC2 or of BAP1 due ...
Mier1 encodes a novel transcriptional regulator and was originally isolated as a fibroblast growth factor early response gene. Two major protein isoforms have been identified, MIER1α and β, which differ in their C-terminal sequence. Previously, we demonstrated that both isoforms recruit histone deacetylase 1 (HDAC1) to repress transcription. To further explore the role of MIER1 in chromatin remodeling, we investigated the functional interaction of MIER1 with the histone acetyltransferase (HAT), Creb-binding protein (CBP). Using GST pull-down assays, we demonstrate that MIER1 interacts with CBP and that this interaction involves the N-terminal half (amino acids 1-283) of MIER1, which includes the acidic activation and ELM2 domains and the C-terminal half (amino acids 1094-2441) of CBP, which includes the bromo-, HAT, C/H3 and glutamine-rich domains. Functional analysis, using HEK293 cells, shows that the CBP bound to MIER1 in vivo has no ...
1. Jain N, Odenike O. Emerging role of the histone deacetylase inhibitor romidepsin in hematologic malignancies. Expert Opin Pharmacother. 2010;11:3073-84 2. Zain J, OConnor OA. Targeting histone deacetyalses in the treatment of B- and T-cell malignancies. Invest New Drugs. 2010;28(Suppl 1):S58-78 3. Haberland M, Montgomery RL, Olson EN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet. 2009;10:32-42 4. Watanabe T. Investigational histone deacetylase inhibitors for non-Hodgkin lymphomas. Expert Opin Investig Drugs. 2010;19:1113-27 5. Buglio D, Younes A. Histone deacetylase inhibitors in Hodgkin lymphoma. Invest New Drugs. 2010;28(Suppl 1):S21-7 6. Copeland A, Buglio D, Younes A. Histone deacetylase inhibitors in lymphoma. Curr Opin Oncol. 2010;22:431-6 7. Mithraprabhu S, Grigoriadis G, Khong T. et al. Deacetylase inhibition in ...
Covalent modification of histone tails is a major epigenetic mechanism. Furthermore, multiple intra-nucleosomal or inter-nucleosomal histone modifications are frequently observed within the same genomic loci. The histone code hypothesis postulates that multiple histone modifications act in a combinatorial fashion to specify distinct chromatin states, which in turn regulate gene activities [1, 2]. To completely characterize the histone code is a major goal of epigenetics research.. To date, Chromatin Immunoprecipitation coupled with microarray chip (ChIP-Chip) or deep sequencing (ChIP-Seq) is the predominant experimental technology for obtaining genome-wide maps of histone modifications. However, ChIP-based technologies have inherent resolution limit given the fragmentation limit of chromatin DNA [3]. Recently, mass spectrometry (MS) has been applied to effectively characterize and quantitate combinatorial ...
Similar to AOA treatment, knocking down GOT2 could also effectively inhibit the malate-aspartate shuttle, resulting in a significant increase (by 1.3‐fold; P , 0.01) in the cytosolic NADH level in Panc‐1 cells (Supplementary Fig S8A). Concomitantly, GOT2 knockdown led to a substantial reduction in the mitochondrial NADH level (by 33%; P , 0.01) (Supplementary Fig S8B), affirming the vital role of GOT2 in controlling the net transfer of cytosolic NADH into mitochondria. As a result, GOT2 knockdown significantly reduced ATP production (by 26%; P , 0.01) in Panc‐1 cells (Supplementary Fig S8C). Moreover, in these stable Panc‐1 cells with GOT2 knockdown, we found that re‐expression of acetylation‐mimetic 3KQ mutant GOT2 led to a significant (P , 0.05) reduction in the cytosolic NADH level as compared to wild‐type‐rescued cells when treated without or with glucose (i.e., 0 and 12 mM glucose) (Fig 4B). Meanwhile, 3KQ mutant GOT2‐rescued cells displayed a significant (P , 0.05 or P , ...
The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and...
Epigenetic alterations of the histone acetylation play an important role in the regulation of gene expression associated with cell cycles and apoptosis that may affect the chemosensitivity of gastric carcinomas. Recently, a histone deacetylase inhibitor, trichostatin A (TSA), was proven to be a chemo-sensitizer on human erythroleukemia cells. With the aim of improving the chemotherapeutic efficacy of gastric carcinoma, the effect of TSA on the chemosensitivity of several anticancer drugs in gastric carcinoma cells was investigated. Human gastric cancer cell lines, OCUM-8 and MKN-74, and 5 anticancer drugs, 5-fluorouracil (5-FU), paclitaxel (PTX), oxaliplatin (OXA), irinotecan (SN38) and gemcitabine (GEM) were used. In both gastric cancer cell lines, a synergistic anti-proliferative effect by the combination of TSA (30 ng/ml) with 5-FU, PTX or SN38 showed a synergistic anti-proliferative effect in OCUM-8 and MKN-74 cells. TSA increases the expression of p21, ...
Pericentric heterochromatin is a highly compacted structure required for accurate chromosome segregation in mitosis. In mammals, it relies on methylation of histone H3K9 by Suv39H enzymes, which provides a docking site for HP1 proteins, therefore mediating heterochromatin compaction. Here we show that, when this normal compaction pathway is defective, the histone acetyltransferase Tip60 is recruited to pericentric heterochromatin, where it mediates acetylation of histone H4K12. Furthermore, in such a context, depletion of Tip60 leads to derepression of satellite transcription, decompaction of pericentric heterochromatin, and defects in chromosome segregation in mitosis. Finally, we show that depletion of BRD2, a double bromodomain-containing protein that binds H4K12ac, phenocopies the Tip60 depletion with respect to heterochromatin decompaction and defects in chromosome segregation. Taking the results ...
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Methods and Results-In the present study, we investigated the role of histone deacetylase (HDAC) inhibition in SMC proliferation and neointimal remodeling. We demonstrate that mitogens induce transcription of HDAC 1, 2, and 3 in SMC. Short interfering RNA-mediated knockdown of either HDAC 1, 2, or 3 and pharmacological inhibition of HDAC prevented mitogen-induced SMC proliferation. The mechanisms underlying this reduction of SMC proliferation by HDAC inhibition involve a growth arrest in the G1 phase of the cell cycle that is due to an inhibition of retinoblastoma protein phosphorylation. HDAC inhibition resulted in a transcriptional and posttranscriptional regulation of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip. Furthermore, HDAC inhibition repressed mitogen-induced cyclin D1 mRNA expression and cyclin D1 promoter activity. As a result of this differential cell cycle-regulatory gene expression by HDAC inhibition, the retinoblastoma protein ...
Packaging DNA into chromatin is dynamic, reversible, and essential for eukaryotic cell viability. The principal packaging unit of chromatin is the nucleosome, consisting of an octamer of two copies each of the four canonical histones (H2A, H2B, H3, and H4) wrapped in 146 bp of DNA (1). Histone proteins are decorated with posttranslational modifications, including lysine acetylation, which influence chromatin architecture by altering nucleosome contacts or by affecting interactions with nonhistone proteins (2). During DNA-dependent processes, nucleosomes disassemble to grant access to specific regions of DNA and reassemble in a way that preserves the local chromatin landscape. By virtue of their highly basic charge, histones are prone to both aggregation and promiscuous interactions when they are not associated with DNA, such as when they are newly synthesized or during nucleosome turnover. ...
N-terminal acetyltransferase (Nats) complex is responsible for protein N-terminal acetylation (Nα-acetylation), which is one of the most common covalent modifications of eukaryotic proteins. Although genome-wide investigation and characterization of Nat catalytic subunits (CS) and auxiliary subunits (AS) have been conducted in yeast and humans they remain unexplored in plants. Here we report on the identification of eleven genes encoding eleven putative Nat CS polypeptides, and five genes encoding five putative Nat AS polypeptides in Populus. We document that the expansion of Nat CS genes occurs as duplicated blocks distributed across 10 of the 19 poplar chromosomes, likely only as a result of segmental duplication events. Based on phylogenetic analysis, poplar Nat CS were assigned to six subgroups, which corresponded well to the Nat CS types (CS of Nat A-F), being consistent with previous reports in humans and yeast. In silico analysis of ...
Binding of epidermal growth factor (EGF) to its receptor leads to receptor dimerization, assembly of protein complexes, and activation of signaling networks that control key cellular responses. Despite their fundamental role in cell biology, little is known about protein complexes associated with the EGF receptor (EGFR) before growth factor stimulation. We used a modified membrane yeast two-hybrid system together with bioinformatics to identify 87 candidate proteins interacting with the ligand-unoccupied EGFR. Among them was histone deacetylase 6 (HDAC6), a cytoplasmic lysine deacetylase, which we found negatively regulated EGFR endocytosis and degradation by controlling the acetylation status of α-tubulin and, subsequently, receptor trafficking along microtubules. A negative feedback loop consisting of EGFR-mediated phosphorylation of HDAC6 Tyr570 resulted in reduced deacetylase activity and increased ...
The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at "entry sites" that contain a consensus sequence motif ("MSL recognition element" or MRE). However, this motif is only similar to 2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex) and female Kc cells (which lack the complex), we find that the presence of active ...
purpose. To characterize the molecular sequelae induced in retinoblastoma (Rb) cells by histone deacetylase inhibitors (HDACIs). Hydroxamic acid-based HDACIs such as vorinostat (suberoylanilide hydroxamic acid) induce the differentiation and apoptosis of transformed cells. Vorinostat has demonstrated significant anticancer activity against hematologic and solid tumors at doses well tolerated by patients and has been approved for the treatment of patients with cutaneous T-cell lymphoma.. methods. The authors evaluated the effects of the HDACIs vorinostat and m-carboxycinnamic acid bis-hydroxamide on the Rb cell lines Y79 and WERI-Rb1 with the use of the MTT assay, BrdU incorporation assay, flow cytometry, immunoblotting, gene-expression profiling, quantitative RT-PCR, and NF-κB DNA-binding assay.. results. Both HDACIs were effective against both Rb cell lines, inducing growth arrest and apoptosis in vitro. Vorinostat increased p53 expression and activated caspases -8, -9 and -3, whereas ...
The identification of demethylase enzymes has revealed that histone methylation can be dynamically regulated in a manner similar to that of histone acetylation and phosphorylation. In S. cerevisiae, the enzymes that place histone methylation marks are well characterized and coordinate mainly the addition of these modifications during the process of active transcription (25). Previously, only one histone demethylase enzyme, Jhd1, was identified in budding yeast. Jhd1 is a JmjC-domain-containing protein that catalyzes the demethylation of H3K36me2 and H3K36me1 modification states (36). Given that Jhd1 does not target H3K36me3 in yeast, it remained possible that this methylation state was irreversible.. Here, we identify Rph1 as being a histone demethylase with activity towards histone H3K36me3 and H3K36me2 modification states. Deletion of RPH1 does not affect global ...
Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for ...
Over the past two decades, epigenetics has evolved into a key concept for understanding regulation of gene expression. Among many epigenetic mechanisms, covalent modifications such as acetylation and methylation of lysine residues on core histones emerged as a major mechanism in epigenetic regulation. Here, we present the database for histone-modifying enzymes (dbHiMo; http://hme.riceblast.snu.ac.kr/) aimed at facilitating functional and comparative analysis of histone-modifying enzymes (HMEs). HMEs were identified by applying a search pipeline built upon profile hidden Markov model (HMM) to proteomes. The database incorporates 11 576 HMEs identified from 603 proteomes including 483 fungal, 32 plants and 51 metazoan species. The dbHiMo provides users with web-based personalized data browsing and analysis tools, supporting comparative and evolutionary genomics. With comprehensive data entries and associated web-based tools, our database will ...
Histone acetyltransferases serve many biological roles inside the cell. Chromatin is a combination of proteins and DNA found in the nucleus, and it undergoes many structural changes as different cellular events such as DNA replication, DNA repair, and transcription occur.[22] Chromatin in the cell can be found in two states: condensed and uncondensed. The latter, known as euchromatin, is transcriptionally active, whereas the former, known as heterochromatin, is transcriptionally inactive.[22][23] Histones comprise the protein portion of chromatin. There are five different histone proteins: H1, H2A, H2B, H3, and H4. A core histone is formed when two of each histone subtype, excluding H1, form a quaternary complex. This octameric complex, in association with the 147 base pairs of DNA coiled around it, forms the nucleosome.[3] Histone H1 locks the nucleosome ...
A HDAC inhibitor Trichostatin A (TSA) induced apoptosis in the presence of survival-prolonging cytokines interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF) in eosinophils and neutrophils. TSA enhanced constitutive eosinophil and neutrophil apoptosis. Similar effects were seen with a structurally dissimilar HDAC inhibitor apicidin. TSA showed additive effect on the glucocorticoid-induced eosinophil apoptosis, but antagonized glucocorticoid-induced neutrophil survival. Eosinophils and neutrophils expressed all HDACs at the mRNA level except that HDAC5 and HDAC11 mRNA expression was very low in both cell types, HDAC8 mRNA was very low in neutrophils and HDAC9 mRNA low in eosinophils. TSA reduced eosinophil and neutrophil nuclear HDAC activities by ~50-60%, suggesting a non-histone target. However, TSA did not increase the acetylation of a non-histone target NF-κB p65. c-jun-N-terminal kinase and caspases 3 and 6 may be involved in the ...
DNA is wrapped around a histone octamer to form the basic unit of chromatin structure. During embryogenesis, dynamic changes of chromatin structure and chromatin modification occur after fertilization; subsequently, the epigenetic information is inherited through many rounds of the cell cycle. Thus, chromatin is essential for the determination of cell identity. Two strategies are used to modulate a chromatin environment: the covalent modification of histone tails and energy-dependent chromatin remodeling. The acetylation, methylation or phosphorylation of histone tails can have profound effects on chromatin structure and transcription (Jenuwein and Allis, 2001). Chromatin remodeling reactions are catalyzed by large protein complexes that use the energy of ATP hydrolysis to alter the structure or positioning of nucleosomes (Becker and Hörz, 2002; Clapier and Cairns, 2009). In addition to these events, histone ...
The connective tissue growth factor gene (CTGF) is aberrantly expressed in 75% of precursor B-cell acute lymphoblastic leukaemias (pre-B ALL) and is associated with poor outcome. We identified consistent hypomethylation of the CTGF locus in primary pre-B ALL specimens regardless of CTGF expression. By contrast, primary T-cell ALL specimens, which do not express CTGF, exhibited distinctive patterns of hypermethylation. Furthermore, we confirmed that global changes in DNA methylation and histone acetylation can both functionally modulate CTGF expression in pre-B ALL cell lines. These data suggest that hypomethylation of the CTGF locus is an essential prerequisite for aberrant CTGF expression in pre-B ALL.. ...
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References for Abcams Recombinant Human SIRT4 protein (ab79949). Please let us know if you have used this product in your publication
Buy our Recombinant Human SIRT4 protein. Ab101713 is a full length protein produced in Escherichia coli and has been validated in SDS-PAGE. Abcam provides free…
The field of cancer epigenetics has received much attention in recent years. However, the relationship of cancer epigenetics with cancer etiology is not clear. Recent studies suggest the involvement of altered DNA methylation and histone modifications in the emergence of epigenetically reprogrammed cells with specific tumor-related phenotypes at premalignant stages of tumor development. In this study, we used a methyl-deficient model of rodent hepatocarcinogenesis to examine the roles of DNA, histone H3 lysine 9 and histone H4 lysine 20 methylation, and the level of the expression of Suv39h1 and Suv4-20h2 histone methyltransferases in the carcinogenic process. We demonstrated that the development of liver tumors was characterized by progressive demethylation of DNA repeats, decrease in histone H4 lysine 20 trimethylation, and a gradual decrease in the expression of Suv4-20h2 histone methyltransferase. A ...
Figure 1. HDAC inhibition by TSA in MA-11 cells-histone acetylation and poly(ADP-ribose) polymerase protein status. The cells were treated with TSA at increasing concentrations (top) or at 300 nmol/L (+), or left untreated (−; bottom). Protein extracts prepared after 6 to 24 h of incubation were analyzed by Western blot hybridization with an antibody against acetylated histone H4 (acetyl-H4) or an anti-poly(ADP-ribose) polymerase (PARP) antibody that binds with higher affinity to the poly(ADP-ribose) polymerase cleavage fragment (85 kDa) than to the uncleaved fragment (116 kDa). Bottom, included is a protein extract from MA-11 cells treated (+) with 10 ng/mL of a Pseudomonas exotoxin A-containing immunotoxin (IT), used as positive control for poly(ADP-ribose) polymerase cleavage (21). Expression of α-tubulin was measured as loading control. ...
Acetic anhydride, is a colorless liquid, primarily used in the manufacturing of cellulose acetate. Cellulose acetate is used in production of several products, such as cigarette filters, textile fibers and plastic goods. In addition, acetic anhydride is used for production or manufacturing of resins & polymers, artificial sweeteners, TAED, explosives, agrochemicals, coating materials and others. Acetic anhydride is used to manufacture tetraacetylethylenediamine (TAED), which is utilized as a bleach activator in laundry and cleaning industry. Similarly, acetic anhydride, in addition to its several other applications, is used often in the form of derivatives or sources, amongst which cellulose acetate is the most widely used derivative.. Cigarette filters, occupy the largest share in volume, since their tar and nicotine removal rate goes up to 50%, higher than other compounds such as phenols. Thus, cellulose acetate contributes to more than half of the world acetic anhydride market. The demand for ...
Alginate can be produced by a microbial fermentation using bacteria such as Azobacter Vinelandii and Pseudomonas Aeruginosa (Linker and Jones 1964, Gorin and Spencer 1966). These bacteria produce a polysaccharide with a structure resembling alginate, differing only in that there are acetyl groups on a portion of the C2 and C3 hydroxyls. It is believed that the acetate groups are associated mainly with the D-mannuronic acid residues (Davidson 1977, Sutherland 1983, Paul 1986). The level of acetylation is variable as is the mannuronic and guluronic acid content. However the level of guluronic acid in the final polymer can be controlled to some extent by altering the level of calcium in the fermentation broth (Haug and Larsen 1971). The sequence structures and acetylation patterns of bacterial alginate, from different sources, have been studied with 2D COSY proton NMR techniques. The acetyl residues were found to be exclusively associated with the mannuronic acid residues with ...
Histone modifications play critical roles in regulating both global and stage-specific gene expression. Methylation on histones H3K4, H3K36 and H3K79 is generally associated with gene activation, whereas methylation on histones H3K9 and H3K27 is generally associated with gene repression. Histone lysine methylation is dynamically regulated by site-specific methyltransferases and demethylases. EZH2 (the catalytic subunit of PRC2) is responsible for the methylation of H3K27 in cells.. DOT1L is a histone H3 lysine 79 methyltransferase whose inhibition increases the yield of induced pluripotent stem cells (iPSCs). EPZ-5676 is a potent and selective DOT1L inhibitor.. Crucial to PRC2 activity, the histone methyltransferase enhancer of zeste homolog 2 (EZH2) tri-methylates lysine 27 of histone 3 (H3K27me3), leading to chromatin condensation and transcriptional repression.. ...
The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels. While expression of AML1-ETO in myeloid differentiated induced pluripotent stem cells (iPSCs) induces leukemic characteristics, overexpression increases cell death. We find that expression of wild-type transcription factors RUNX1 and ERG in AML is required to prevent this oncogene ...
The unfolded protein response (UPR) is an evolutionarily conserved mechanism whereby cells respond to stress conditions that target the endoplasmic reticulum (ER). One of the major targets of the UPR is the 78kDa Glucose Regulated Protein Grp78 (BiP). The transcriptional activation of the promoter of GRP78 has been used extensively as an indicator of the onset of the UPR. The transcriptional activation of Grp78 in response to ER stress has been well documented. It is characterized by multiple transcription factors such as YY1, TFII-I, ATF6(N), and NF-Y binding to conserved promoter sequences at the onset of ER stress.; There are also epigenetic changes that occur during the activation of the Grp78 promoter. We have observed ER-stress induced binding of the histone acetyltransferase p300 to the Grp78 promoter and histone H4 acetylation. We have also seen the arginine methyltransferase PRMT1, and evidence of its action through ...
The unfolded protein response (UPR) is an evolutionarily conserved mechanism whereby cells respond to stress conditions that target the endoplasmic reticulum (ER). One of the major targets of the UPR is the 78kDa Glucose Regulated Protein Grp78 (BiP). The transcriptional activation of the promoter of GRP78 has been used extensively as an indicator of the onset of the UPR. The transcriptional activation of Grp78 in response to ER stress has been well documented. It is characterized by multiple transcription factors such as YY1, TFII-I, ATF6(N), and NF-Y binding to conserved promoter sequences at the onset of ER stress.; There are also epigenetic changes that occur during the activation of the Grp78 promoter. We have observed ER-stress induced binding of the histone acetyltransferase p300 to the Grp78 promoter and histone H4 acetylation. We have also seen the arginine methyltransferase PRMT1, and evidence of its action through ...
One of the longest standing problems in DNA repair is how cells relax chromatin in order to make DNA lesions accessible for global nucleotide excision repair (NER). Since chromatin has to be relaxed for efficient lesion detection, the key question is whether chromatin relaxation precedes lesion detection or vice versa. Chromatin accessibility factors have been proposed but not yet identified. Here we show that p53 acts as a chromatin accessibility factor, mediating UV-induced global chromatin relaxation. Using localized subnuclear UV irradiation, we demonstrate that chromatin relaxation is extended over the whole nucleus and that this process requires p53. We show that the sequence for initiation of global NER is as follows: transcription-associated lesion detection; p53-mediated global chromatin relaxation; and global lesion detection. The tumour suppressor p53 is crucial for genomic stability, a role partially explained by its pro-apoptotic capacity. We demonstrate here that p53 is also a ...
Silent information regulator 1 (SIRT), also known as NAD-dependent deacetylase sirtuin, is a member of the class III group of histone deacetylases, collectively called sirtuins. The mammalian sirtuin family consists of 7 members, designated SIRT1 through SIRT7, which are characterized by a conserved 275-amino-acid catalytic core and unique additional N-terminal and C-terminal sequences of variable length. Previous studies have shown that SIRT can deacetylate many transcription factors, including forkhead box O (FOXO) transcription factors, p53, nuclear factor-κB (NF-κB), liver X receptor (LXR), and nuclear co-activators, as well, including peroxisome proliferator-activated receptor γcoactivator-1α(PGC-1α), cAMP-responsive element-binding protein-regulated transcription co-activator 2, and period homolog 2. It has been reported that SIRT family perform a wide variety of functions in a variety of biological systems, including obesity-associated metabolic diseases, endocrine ...
Brain tumor news: A phase I/II trial of the histone deacetylase inhibitor, romidepsin, for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03.
Covalent modifications of histones and histone variants have great influence on chromatin structure, which is involved in the transcriptional regulation of gene expression. Chromatin immunoprecipitation (ChIP) is a powerful tool for studying in vivo DNA-histone interactions. Strawberry is a model for Rosaceae and non-climacteric fruits, in which histone modifications have been implicated to affect fruit development and ripening. However, a validated ChIP method has not been reported in strawberry, probably due to its high levels of polysaccharides which affect the quality of prepared chromatin and the efficiency of immunoprecipitation. We describe a native chromatin immunoprecipitation (N-ChIP) protocol suitable for strawberry by optimizing the parameters for nuclei isolation, chromatin extraction, DNA fragmentation and validation analysis using quantitative real-time PCR (qRT-PCR). The qRT-PCR results show that both the active mark H3K36me3 ...
Aberrant acetylation has been strongly linked to tumorigenesis, and the modulation of acetylation through targeting histone deacetylases (HDACs) is gathering increasing pace as a viable therapeutic strategy. A genome-wide loss-of-function screen identified HR23B, which shuttles ubiquitinated cargo proteins to the proteasome, as a sensitivity determinant for HDAC inhibitor-induced apoptosis. HR23B also governs tumor cell sensitivity to drugs that act directly on the proteasome. The level of HR23B influences the response of tumor cells to HDAC inhibitors, and HR23B is found at high levels in cutaneous T cell lymphoma in situ, a malignancy that responds favorably to HDAC inhibitor-based therapy. These results suggest that deregulated proteasome activity contributes to the anticancer activity of HDAC inhibitors.
Deardorff M A, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, Saitoh K, Komata M, Katou Y, Clark D, Cole K E, De Baere E, Decroos C, Di Donato N, Ernst S, Francey L J, Gyftodimou Y, Hirashima K, Hullings M, Ishikawa Y, Jaulin C, Kaur M, Kiyono T, Lombardi P M, Magnaghi-Jaulin L, Mortier G R, Nozaki N, Petersen M B, Seimiya H, Siu V M, Suzuki Y, Takagaki K, Wilde J J, Willems P J, Prigent C, Gillessen-Kaesbach G, Christianson D W, Kaiser F J, Jackson L G, Hirota T, Krantz I D, and Shirahige K: HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature.489:313-317, 2012. https://www.ncbi.nlm.nih.gov/pubmed/22885700 ...
Romidepsin (depsipeptide, FR901228, FK228, NSC 630176) is a relatively unique HDACi as it is a prodrug. Upon entering cells romidepsin is reduced to an active compound, capable of preferentially interacting with the zinc in the active site of the HDAC class I enzymes, however, it is still generally classified as a broad-spectrum inhibitor as it does inhibit class II enzymes (31).. A dose escalation study in chronic lymphocytic leukemia (CLL) and AML patients was done by Byrd and colleagues, with the aim of achieving an in vivo dose that increased acetylation of histone proteins H3 and H4 by 100% in vitro (32). Although no formal CR or partial responses (PR) were seen in 10 CLL patients, antitumor activity was noted. Of 10 patients with AML none achieved CR or PR although one patient experienced tumor lysis syndrome. Another study with 11 AML/myelodysplasia (MDS) patients had one CR with SD in six patients (33). Correlative studies showed a modest but rapid ...
PRIMARY OBJECTIVES:. I. To evaluate the safety and toxicity of vorinostat in combination with azacitidine in patients with myelodysplastic syndromes (MDS) and some select patients with acute myeloid leukemia (AML) (step 1).. II. To identify doses of both vorinostat and azacitidine for safe combination of the 2 agents that can be administered in repetitive cycles over time for use in phase II studies.. III. To determine the response rate of patients treated with the combination of suberoylanilide hydroxamic acid (SAHA) (vorinostat) and azacitidine at the doses established as safe and effective in Step 1 in an expanded cohort of patients with MDS.. IV. To obtain preliminary data on the effects of treatment with the combination of vorinostat and Aza C (azacitidine) in patients with MDS on a series of biologic surrogate markers including: deoxyribonucleic acid (DNA) methylation of specific genes (e.g. p15); histone acetylation; hematopoietic progenitor growth and ...
We present depth-resolved spatial-domain low-coherence quantitative phase microscopy, a simple approach that utilizes coherence gating to construct a depth-resolved structural feature vector quantifying sub-resolution axial structural changes at different optical depths within the sample. We show that this feature vector is independent of sample thickness variation, and identifies nanoscale structural changes in clinically prepared samples. We present numerical simulations and experimental validation to demonstrate the feasibility of the approach. We also perform experiments using unstained cells to investigate the nanoscale structural changes in regulated cell proliferation through cell cycle and chromatin decondensation induced by histone acetylation. (C) 2013 Optical Society of ...
Distinct patterns of histone methylation during human cell cycle progression are described. Histone H4 methyltransferase activity is cell cycle-regulated, consistent with increased H4 Lys 20 methylation at mitosis. This increase closely follows the cell cycle-regulated expression of the H4 Lys 20 methyltransferase, PR-Set7. Localization of PR-Set7 to mitotic chromosomes and subsequent increase in H4 Lys 20 methylation were inversely correlated to transient H4 Lys 16 acetylation in early S-phase. These data suggest that H4 Lys 20 methylation by PR-Set7 during mitosis acts to antagonize H4 Lys 16 acetylation and to establish a mechanism by which this mark is epigenetically transmitted (Rice, 2002). To determine histone methyltransferase activity during the human cell cycle, HeLa cells were arrested by treatment with thymidine followed by mimosine. Every 2.5 h following release from the G1 arrest, synchronized cells were ...

Hexavalent Chromium (Cr(VI)) Down-Regulates Acetylation of Histone H4 at Lysine 16 through Induction of Stressor Protein Nupr1Hexavalent Chromium (Cr(VI)) Down-Regulates Acetylation of Histone H4 at Lysine 16 through Induction of Stressor Protein Nupr1

Histone acetyltransferase MOF forms a complex with MSL1 and MSL3 proteins and specifically acetylates H4K16 [39]. Interestingly ... Nupr1 is required for metastasis of breast cancer [19]. Nupr1 was also found over-expressed in thyroid neoplasm and its ... A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at ... hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells. Mol Cell Biol. 2005;25(15): ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC4902237/

Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells.Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells.

... of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated ... represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcriptionJ Biol ... Breast Neoplasms / genetics, metabolism*, pathology. CREB-Binding Protein / metabolism. Cell Cycle / drug effects. Cell ... 0/Antineoplastic Agents; 0/CREBBP protein, human; 0/Enzyme Inhibitors; 0/H2AFX protein, human; 0/Histones; 0/TP53 protein, ...
more infohttp://www.biomedsearch.com/nih/Differential-effects-garcinol-curcumin-histone/23356739.html

Proline Rich Motifs as Drug Targets in Immune Mediated DisordersProline Rich Motifs as Drug Targets in Immune Mediated Disorders

... metal-binding proteins, and ribosomal proteins suggesting an evolutionary conservation of protein-protein networks centered on ... The acetylation of critical lysine residues of p53 by the histone acetyltransferase activity of p300 then promotes the ... Although the pathological role of p53 in many neoplasms has been well characterized, the mechanisms of DNA damage and the ... 1. Protein-Protein Interactions. Protein-protein interactions (PPIs) are critical for most biological functions and cellular ...
more infohttps://www.hindawi.com/journals/ijpep/2012/634769/

KAT5 | Cancer Genetics WebKAT5 | Cancer Genetics Web

... transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase ... histone acetylation - histone acetyltransferase activity - metal ion binding - negative regulation of interleukin-2 production ... genetic analysis is now a routine ancillary diagnostic modality to the histopathological diagnosis of soft-tissue neoplasms, ... A histone acetyltransferase Tat-interacting protein 60 kDa (Tip60) regulates the DNA damage response by acetylating histone and ...
more infohttp://www.cancerindex.org/geneweb/KAT5.htm

Journal: Molecular cell / Publication Year: 2017 / Source: 2017 v.67 no.2 - PubAg Search ResultsJournal: Molecular cell / Publication Year: 2017 / Source: 2017 v.67 no.2 - PubAg Search Results

DNA-directed RNA polymerase; acetylation; epigenetics; genes; heterochromatin; histone acetyltransferase; histones; neoplasms; ... 8. Msp1 Is a Membrane Protein Dislocase for Tail-Anchored Proteins Author:. Wohlever, Matthew L.; Mateja, Agnieszka; McGilvray ... DNA damage; DNA repair; acetyl coenzyme A; acetylation; histones; metabolism; tumor suppressor proteins. Abstract:. ... In this ... Since histone acetylation plays important roles in DNA repair and is sensitive to the availability of acetyl coenzyme A (acetyl ...
more infohttps://pubag.nal.usda.gov/?f%5Bjournal_name%5D%5B%5D=Molecular+cell&f%5Bpublication_year_rev%5D%5B%5D=7983-2017&f%5Bsource%5D%5B%5D=2017+v.67+no.2

NAVER Academic | Histone acetyltransferases: function, structure, and catalysisNAVER Academic | Histone acetyltransferases: function, structure, and catalysis

... and genetic studies suggest cross-talk between acetylation and other histone modifications. Developmental aberrations in mice ... Recent structure/function studies provide insights into HAT catalysis and histone binding, ... Histone acetyltransferases (HATs) directly link chromatin modification to gene activation. ... Histone Acetyltransferases, Histones, Humans, Mice, Neoplasms, etiology, Saccharomyces cerevisiae Proteins, Transcription, ...
more infohttps://academic.naver.com/article.naver?doc_id=142738603

Epigenetic mechanisms in respiratory muscle dysfunction of patients with chronic obstructive pulmonary disease.  - PubMed - NCBIEpigenetic mechanisms in respiratory muscle dysfunction of patients with chronic obstructive pulmonary disease. - PubMed - NCBI

... histone acetyltransferases (HATs) and deacetylases (HDACs), total DNA methylation and protein acetylation, small ubiquitin- ... Mean values and standard deviation (protein levels) of total lysine-acetylated proteins and (relative expression) of nuclear ... In diaphragm muscle specimens (thoracotomy due to lung localized neoplasms) of sedentary patients with mild-to-moderate and ... Protein levels of total acetyl-lysine protein content and mRNA levels of the HAT p300 in the diaphragms of COPD patients and ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/25369292?dopt=Abstract

US Patent # 9,890,136. Selective HDAC6 inhibitors - Patents.comUS Patent # 9,890,136. Selective HDAC6 inhibitors - Patents.com

HDAC6 substrates include a number of proteins, eg. tubulin, peroxidases, certain DNA repair proteins, but not histones. HDAC6 ... Heat shock protein 90 (Hsp90) is an important chaperone protein involved in protein folding and is overexpressed in many cancer ... Example 9. Acetylation of Alpha-Tubulin vs. Histones In normal (HFS) and transformed (LNCAP) cells, compound 8, at 8 .mu.M to ... Malignant neoplasms are further exemplified by sarcomas (such as osteosarcoma and Kaposis sarcoma). In some embodiments, a ...
more infohttp://patents.com/us-9890136.html

Novel Histone Deacetylase Inhibitors in the Treatment of Thyroid Cancer | Clinical Cancer ResearchNovel Histone Deacetylase Inhibitors in the Treatment of Thyroid Cancer | Clinical Cancer Research

Induction of p21 mRNA by SAHA involves changes in promoter-associated proteins, including acetylation of core proteins, ... Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms ... Protein loading was monitored by Coomassie blue. B, dose-response experiment for levels of acetylated H3 in FRO cells treated ... The turnover of histone acetylation is regulated by the opposing activities of histone acetyltransferases and histone ...
more infohttp://clincancerres.aacrjournals.org/content/11/10/3958

College of Medicine - Research Output
     - National Cheng Kung UniversityCollege of Medicine - Research Output - National Cheng Kung University

Inhibitor of Apoptosis Proteins Post Translational Protein Processing Acetylation Drug Resistance PubMed ... Targeting histone deacetylase in cancer therapy. Lin, H. Y., Chen, C-S., Lin, S. P., Weng, J. R. & Chen, C. S., 2006 Jul 1, In ... Targeting promyelocytic leukemia protein: A means to regulating PML nuclear bodies. Reineke, E. L. & Kao, H. Y., 2009 Jan 1, In ... The emerging role of hepatitis B virus Pre-S2 deletion mutant proteins in HBV tumorigenesis. Su, I. J., Wang, L. H. C., Hsieh, ...
more infohttps://researchoutput.ncku.edu.tw/en/organisations/college-of-medicine/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Fsystematicreview&ordering=type&descending=false&page=8

Transcriptional Control of Cellular Metabolism by mTOR Signaling | Cancer ResearchTranscriptional Control of Cellular Metabolism by mTOR Signaling | Cancer Research

ATP-citrate lyase links cellular metabolism to histone acetylation. Science 2009;324:1076-80. ... Rheb is a Ras-related small G protein that, when in its GTP-bound state, is a potent and essential activator of mTORC1. In ... SREBP stimulates the expression of genes involved in the synthesis of isoprenoids, which modify many signaling proteins, ... and human neoplasms of the breast, endometrium, cervix, lung, and prostate (37-41). Through the production of NADPH, ...
more infohttp://cancerres.aacrjournals.org/content/71/8/2815.full

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Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases EP300 and KAT2B. Acetylation results in reduced ... response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary ... Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. ... Protein Kinase B Alpha; Protein kinase B; Proto-oncogene c-Akt; RAC Alpha; RAC alpha serine/threonine protein kinase; RAC; RAC ...
more infohttp://www.bioon.com.cn/antibody/Show_product.asp?id=3458372

Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel...Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel...

EPLIN, epithelial protein lost in neoplasm. Oncogene. 1999;18:7838-41.View ArticlePubMedGoogle Scholar. ... Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein ... Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol Cell. 2004;13:627-38.View Article ... RTF1 is critical for histone and chromatin modifications and telomeric silencing [34,35]. Another link with telomere ...
more infohttps://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1283-0

KCTD11 Gene - GeneCards | KCD11 Protein | KCD11 AntibodyKCTD11 Gene - GeneCards | KCD11 Protein | KCD11 Antibody

Protein Coding), Potassium Channel Tetramerization Domain Containing 11, including: function, proteins, disorders, pathways, ... Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. ( ... brain neoplasm, infratentorial. - elite association - COSMIC cancer census association via MalaCards Search KCTD11 in MalaCards ... Protein Symbol:. Q693B1-KCD11_HUMAN. Recommended name:. BTB/POZ domain-containing protein KCTD11. Protein Accession:. Q693B1. ...
more infohttps://www.genecards.org/cgi-bin/carddisp.pl?gene=KCTD11

SIRT7, H3K18ac, and ELK4 Immunohistochemical Expression in Hepatocellular CarcinomaSIRT7, H3K18ac, and ELK4 Immunohistochemical Expression in Hepatocellular Carcinoma

Histone modification involves post-translational modification of N-terminal tails of histone proteins by acetylation, ... They have reported that SIRT7 can regulate protein folding in mitochondria, and a decrease in SIRT7 could result in stem cell ... Hepatocellular carcinoma (HCC) is the sixth most prevalent neoplasm and is the second most common cause of cancer-related death ... Some authors have argued that gene-specific expression of histone acetylation can run contrary to the overall state of ...
more infohttps://www.jpatholtm.org/journal/view.php?number=16625

RUNX1 - WikipediaRUNX1 - Wikipedia

These domains are necessary for RUNX1 to mediate DNA binding and protein-protein interactions respectively. The transcription ... This is further characterized histologically by the presence of Auer rods and epigenetically by lysine acetylation on residues ... Examples range from RUNX1 point mutations acquired from low-dose radiation leading to myelodysplastic neoplasms (MDN) or ... RUNX proteins form a heterodimeric complex with CBFβ which confers increased DNA binding and stability to the complex. ...
more infohttps://en.wikipedia.org/wiki/RUNX1

Frontiers | Progression on Citrullination of Proteins in Gastrointestinal Cancers | OncologyFrontiers | Progression on Citrullination of Proteins in Gastrointestinal Cancers | Oncology

This kind of protein modification was first discovered in autoimmune diseases such as rheumatoid arthritis. The citrullination ... A well-known citrullination of histone involves the key mechanism of neutrophil extracellular traps (NETs) of inflammation in ... Citrullinated proteins disturbed the stability of proteins and caused DNA damages. There is increasing evidence that ... Citrullinated proteins disturbed the stability of proteins and caused DNA damages. There is increasing evidence that ...
more infohttps://www.frontiersin.org/articles/10.3389/fonc.2019.00015/full

DNA Methylation and Chromatin Remodeling: The Blueprint of Cancer EpigeneticsDNA Methylation and Chromatin Remodeling: The Blueprint of Cancer Epigenetics

Of the many groups of proteins belonging to the family of histone acetylation readers, recent studies have illustrated that the ... C. Choudhary, C. Kumar, F. Gnad et al., "Lysine acetylation targets protein complexes and co-regulates major cellular functions ... "Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms," Cancer Research, vol ... Histone Acetylation: An Untapped Gravy Train. Histone acetylation, a very dynamic histone modifying interaction, is carried out ...
more infohttps://www.hindawi.com/journals/scientifica/2016/6072357/

Printing...Printing...

... that regulate the acetylation of histone and nonhistone proteins.4 The acetylation status of these proteins greatly influences ... The peripheral T-cell lymphomas (PTCLs) are a diverse group of mature T-cell neoplasms that typically display aggressive clini- ... thereby affecting protein expression in a manner that could promote malignant behavior. Although lymphomagenesis is complex, ... Glozak MA, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histone proteins. Gene. 2005;363:15-23. ...
more infohttp://www.gotoper.com/print_pub.php?url=/publications/ajho/2014/2014Sep/Belinostat-for-Peripheral-T-Cell-Lymphoma

Dartmouth Digital Library ProgramDartmouth Digital Library Program

Protein kinases -- Mechanism of action. Sodium channels -- Genetic aspects. Glucocorticoids. Acetylation. Histones. Sgk protein ... Medical Terms: TP63 protein, human; Tumor Suppressor Proteins -- genetics; Breast Neoplasms --.... * Efforts to elucidate the ... These protein products are members of the p53 family of transcription factors due to strong structural similarity with... ... Role of Whi3 protein aggregation behavior in cell-cycle regulation and cell polarity / by ChangHwan Lee. ...
more infohttps://libarchive.dartmouth.edu/cdm/search/searchterm/MCF10A/mode/all/order/title

Carcinogenesis - WikipediaCarcinogenesis - Wikipedia

Known mechanisms of epigenetic change include DNA methylation, and methylation or acetylation of histone proteins bound to ... Oncogenes often produce mitogens, or are involved in transcription of DNA in protein synthesis, which creates the proteins and ... Thus, a clone with a mutation in a tumor suppressor gene or oncogene will expand only in a neoplasm if that mutation gives the ... Epimutations can also occur by acetylation, methylation, phosphorylation or other alterations to histones, creating a histone ...
more infohttps://en.wikipedia.org/wiki/Carcinogenesis

Interlink between Nuclear Receptors, Posttranslational Modifications and the Biological Clock in Health and Diseases | OMICS...Interlink between Nuclear Receptors, Posttranslational Modifications and the Biological Clock in Health and Diseases | OMICS...

On the BMAL1 promoter, PGC-1α binding is accompanied by an increase in histone H3 acetylation and histone 3 lysine 4 ... v-erbA Related Protein EAR-1-Related (EAR-1R); RORs: Retinoid Orphan Receptors; EARs: V-erbA Related Proteins; RARs: Retinoic ... pathways in hematopoietic cells and the disruption of the biological clock has been implicated in hematopoietic neoplasm [136 ... Protein Kinase C; PKA: Protein Kinase A; MKK7: MAP (Mitogen-Activated Protein) Kinase Kinase; MAP: Mitogen-activated Protein; ...
more infohttps://www.omicsonline.org/interlink-between-nuclear-receptor-posttranslational-modifications-and-the-biological-clock-in-health-and-diseases-2157-2518.S14-005.php?aid=14012

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Cytokines such as TNFα and IL-1β, acting via NF-κB, can induce histone acetylation in both a time- and concentration-dependent ... Galactose binding protein (GBP), ribose binding protein (RBP).. 110. Find the value of x in the solution for the system x4yz12 ... In one specific instance, that of reticulum cell sarcoma, the inci- dence of this neoplasm in patients who had been ... Vlasta Molak CHAPTER I. 1992; Koch, 1999; Krinskii and Kokoz, 1973; Rinzel, mRNA surveillance, FLAG, DEAD-box proteins, iso- ...
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Biomolecules  | Free Full-Text | Epigenetic Impact on EBV Associated B-Cell Lymphomagenesis | HTMLBiomolecules | Free Full-Text | Epigenetic Impact on EBV Associated B-Cell Lymphomagenesis | HTML

Histone acetylation is reversed by histone deacetylase (HDAC) activities [1,2,4]. ... C-terminal-binding protein 1 (CtBP1) recruitment by EBNA-3 proteins plays a crucial role [59]. In a separate study, EBNA-3A was ... in EBV-associated neoplasms, the immediate early promoters are shown to be typically hypermethylated along with deposition of ... C-terminal binding protein; HATs: Histone acetyltransferases; HDACs: Histone deacetylases; CDKN2B: Cyclin dependent kinase ...
more infohttps://www.mdpi.com/2218-273X/6/4/46/htm

Class I Histone Deacetylase Expression Has Independent Prognostic Impact in Human Colorectal Cancer: Specific Role of Class I...Class I Histone Deacetylase Expression Has Independent Prognostic Impact in Human Colorectal Cancer: Specific Role of Class I...

Reversible histone acetylation in normal and transformed cells is regulated by histone acetylases and histone deacetylases ( ... Equal protein loading was ascertained by probing against actin. D, selective knockdown of HDAC2 in other colon cancer cell ... As there are known structural homologies between the three proteins, antibody specificity was ascertained by selective short ... regimens used and combination with radiotherapy have considerably improved survival of patients with advanced neoplasms (8), ...
more infohttp://clincancerres.aacrjournals.org/content/14/6/1669
  • This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. (cancerindex.org)
  • The prototypes of this class of compounds, hydroxamic acid-based suberoylanilide hydroxamic acid (SAHA) and m -carboxycinnamic acid bis-hydroxamide (CBHA), cause accumulation of acetylated histones in cultured cells, induce differentiation and/or apoptosis of transformed cells in culture ( 2 - 5 , 10 , 16 , 17 ), and inhibit the growth of tumors in animals ( 14 , 17 ). (aacrjournals.org)
  • SAR studied inhibition of proliferation, induction of differentiation and apoptosis, histone acetylation, and gene expression. (edu.au)
  • Human cytomegalovirus stimulates the synthesis of select Akt-dependent antiapoptotic proteins during viral entry to promote survival of infected monocytes. (upstate.edu)
  • Depsipeptide (FR901228), a fermentation product isolated from Chromobacterium violaceum , has shown biological activity in a phase I trial in patients with refractory neoplasms ( 15 ). (aacrjournals.org)
  • Although changes in the chemotherapeutic regimens used and combination with radiotherapy have considerably improved survival of patients with advanced neoplasms ( 8 ), the current therapeutic concepts, especially for late-stage tumors, are far from being optimal. (aacrjournals.org)
  • In this study we assessed the effects of the phytocompounds garcinol and curcumin on histone and p53 modification in cancer cells, focussing on the breast tumour cell line MCF7. (biomedsearch.com)
  • The citrullination modification (Cit) of proteins has received increasing attention in recent years. (frontiersin.org)
  • This kind of protein modification was first discovered in autoimmune diseases such as rheumatoid arthritis. (frontiersin.org)
  • Further studies revealed that citrullination modification of proteins also involves in carcinogenesis in human being. (frontiersin.org)
  • This review introduces the concept of citrullination modification of proteins, substrate proteins, examining methods and biological significances. (frontiersin.org)
  • Citrullination of proteins is a new kind of post-translational modification, which has been reported to be involved in large numbers of autoimmune diseases and cancers. (frontiersin.org)
  • ATP-citrate lyase links cellular metabolism to histone acetylation. (naver.com)
  • AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. (bioon.com.cn)
  • Citrullination of protein refers to the process by which the peptidyl arginine residue is converted to citrulline by a catalytic enzyme (Figure 1 ). (frontiersin.org)
  • A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase. (wikipedia.org)
  • Interestingly, Cr(VI) exposure also results in the loss of acetylation at histone H4K16, which is considered a 'hallmark' of human cancer. (pubmedcentralcanada.ca)
  • CONCLUSION: In summary, although garcinol and curcumin can both inhibit histone acetyltransferase activities, our results show that these compounds have differential effects on cancer cells in culture. (biomedsearch.com)
  • Hepatocellular carcinoma (HCC) is the sixth most prevalent neoplasm and is the second most common cause of cancer-related death worldwide [ 1 ]. (jpatholtm.org)
  • There is increasing evidence that citrullinated proteins can be used as potential targets for cancer diagnosis or treatment. (frontiersin.org)
  • Homo- or heterologous oligomeric PPI complexes represent isologous or heterologous association of identical protein units. (hindawi.com)
  • The serine/threonine kinase mTOR exists within 2 distinct protein complexes, and we focus here on mTOR complex 1 (mTORC1), which senses the availability of growth factors, nutrients, and cellular stress to coordinate anabolic processes promoting cell growth and proliferation ( 3 ). (aacrjournals.org)
  • A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme. (naver.com)