Jumonji domain containing histone demethylases. Medical search

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.

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.

Oxidoreductases, N-Demethylating are enzymes that catalyze the oxidation of N-methyl groups to carbonyl groups, typically found in xenobiotic metabolism, involving the removal of methyl groups from various substrates using molecular oxygen.

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.

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)

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.

An essential amino acid. It is often added to animal feed.

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.

A retinoblastoma binding protein that is also a member of the Jumonji-domain histone demethylases. It has demethylation activity towards specific LYSINE residues found on HISTONE H3.

A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.

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.

Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.

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.

Enzymes that catalyze acyl group transfer from ACETYL-CoA to HISTONES forming CoA and acetyl-histones.

Formation of an acetyl derivative. (Stedman, 25th ed)

A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer. (1/332)

A novel human gene (PLU-1) has been identified which shows a highly restricted expression in normal adult tissues but which is consistently expressed in breast cancers. A fragment of the PLU-1 cDNA was identified by differentially screening a fetal brain library with cDNAs prepared from ce-1 cells (a human mammary epithelial cell line overexpressing c-ErbB2) treated or untreated with the antibody 4D5, which inhibits c-ErbB2 phosphorylation. Clones covering the full cDNA sequence of 6.4 kilobases were isolated from a breast cancer cDNA library. Although expression of PLU-1 in ce-1 cells is regulated by signaling from c-ErbB2, the gene is expressed in all the breast cancer cell lines examined, in cells cultured from primary breast cancers, and in the invasive and in situ components of primary breast cancers. Translation of the open reading frame predicts a protein of 1544 amino acids, which contains three PHD/LAP motifs, a specific DNA-binding domain found in a Drosophila protein (dri) and novel domains showing extensive homology with other human and non human gene products. Transient transfection of cell lines with MYC-tagged PLU-1 showed the protein to be localized in the nucleus and associated with discrete foci. The presence of the dri motif and PHD/LAP fingers together with the clear nuclear localization and consistent expression in breast cancers, suggest a role for PLU-1 in regulating gene expression in breast cancers. (+info)

Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines. (2/332)

In a recent study, we identified frequent amplification of DNA copy number at chromosome 9p23-24 in cell lines derived from esophageal squamous cell carcinomas (ESCs), using comparative genomic hybridization. Because amplified regions often harbor oncogenes and/or other tumor-associated genes, and because 9p23-24 amplification had been reported in various other types of cancers, we used fluorescence in situ hybridization and Southern blot analysis to map the 9p23-24 amplicon. We then screened target genes/transcripts present within this amplicon by Northern blotting. With this strategy, we successfully cloned a novel gene, designated gene amplified in squamous cell carcinoma 1 (GASC1), that was amplified and overexpressed in several ESC cell lines. The deduced amino acid sequence of GASC1 contains two PHD-finger motifs and a PX domain. PHD-finger motifs are found in nuclear proteins that participate in chromatin-mediated transcriptional regulation and are present in a number of proto-oncogenes. Our findings suggest that overexpressed GASC1 may play an important role in the development and/or progression of various types of cancer including ESC. (+info)

If phosphatidylserine is the death knell, a new phosphatidylserine-specific receptor is the bellringer. (3/332)

Recognition of phosphatidylserine (PtdSer) is essential for engulfment of apoptotic cells by mammalian phagocytes. Engagement of a new phosphatidylserine-specific receptor (PtdSerR) appears to be necessary for uptake of apoptotic cells. Many other mammalian receptors have been described to function in the clearance of apoptotic cells. The emerging picture is that many of these receptors may provide the strong adhesion needed to increase the likelihood of contact between the PtdSerR and its phospholipid ligand, which is required for uptake. Furthermore, stimulation of this receptor on different types of phagocytes by apoptotic cells, PtdSer-containing liposomes or an IgM monoclonal anti-PtdSer antibody initiates release of TGFbeta, known to be involved in the anti-inflammatory effects of apoptotic cells. Although highly homologous genes exist in C. elegans and Drosophila melanogaster, their role in engulfment of apoptotic cells remains to be determined. (+info)

A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31. (4/332)

Interstitial deletion or loss of chromosome 5, del(5q) or -5, is a frequent finding in myeloid leukemias and myelodysplasias, suggesting the presence of a tumor suppressor gene within the deleted region. In our search for this gene, we identified a candidate, 5qNCA (LOC51780), which lies within a consistently-deleted segment of 5q31. 5qNCA expresses a 7.2-kb transcript with a 5286-bp open reading frame which is present at high levels in heart, skeletal muscle, kidney, placenta, and liver as well as CD34+ cells and AML cell lines. 5qNCA encodes a 191-kD nuclear protein which contains a highly-conserved C-terminus containing a zinc finger with the unique spacing Cys-X2-Cys-X7-His-X2-Cys-X2-Cys-X4-Cys-X2-Cys and a jmjC domain, which is often found in proteins that regulate chromatin remodeling. Expression of 5qNCA in a del(5q) cell line results in suppression of clonogenic growth. Preliminary sequence results in AML and MDS samples and cell lines has revealed a possible mutation in the KG-1 cell line resulting in a THR to ALA substitution that has not been found in over 100 normal alleles to date. We propose 5qNCA is a good candidate for the del(5q) tumor suppressor gene based on its predicted function and growth suppressive activities, and suggest that further mutational and functional study of this interesting gene is warranted. (+info)

Tethering and tickling: a new role for the phosphatidylserine receptor. (5/332)

Several receptors are implicated in apoptotic cell (AC) uptake by phagocytic cells; however, their relative dominance in mammalian systems remains to be established. New studies shed light on the role of the phosphatidyl serine (PS) receptor (PSR). Ligation of PSR by PS on AC surfaces is considered essential for signaling uptake of ACs that are tethered to phagocytes via other receptors. (+info)

Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. (6/332)

Efficient phagocytosis of apoptotic cells is important for normal tissue development, homeostasis, and the resolution of inflammation. Although many receptors have been implicated in the clearance of apoptotic cells, the roles of these receptors in the engulfment process have not been well defined. We developed a novel system to distinguish between receptors involved in tethering of apoptotic cells versus those inducing their uptake. Our results suggest that regardless of the receptors engaged on the phagocyte, ingestion does not occur in the absence of phosphatidylserine (PS). Further, recognition of PS was found to be dependent on the presence of the PS receptor (PSR). Both PS and anti-PSR antibodies stimulated membrane ruffling, vesicle formation, and "bystander" uptake of cells bound to the surface of the phagocyte. We propose that the phagocytosis of apoptotic cells requires two events: tethering followed by PS-stimulated, PSR-mediated macropinocytosis. (+info)

Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. (7/332)

Cystic fibrosis is characterized by an early and sustained influx of inflammatory cells into the airways and by release of proteases. Resolution of inflammation is normally associated with the orderly removal of dying apoptotic inflammatory cells through cell recognition receptors, such as the phosphatidylserine receptor, CD36, and alpha v integrins. Accordingly, removal of apoptotic inflammatory cells may be impaired in persistent inflammatory responses such as that seen in cystic fibrosis airways. Examination of sputa from cystic fibrosis and non-cystic fibrosis bronchiectasis patients demonstrated an abundance of apoptotic cells, in excess of that seen in patients with chronic bronchitis. In vitro, cystic fibrosis and bronchiectasis airway fluid directly inhibited apoptotic cell removal by alveolar macrophages in a neutrophil elastase-dependent manner, suggesting that elastase may impair apoptotic cell clearance in vivo. Flow cytometry demonstrated that neutrophil elastase cleaved the phosphatidylserine receptor, but not CD36 or CD32 (Fc gamma RII). Cleavage of the phosphatidylserine receptor by neutrophil elastase specifically disrupted phagocytosis of apoptotic cells, implying a potential mechanism for delayed apoptotic cell clearance in vivo. Therefore, defective airway clearance of apoptotic cells in cystic fibrosis and bronchiectasis may be due to elastase-mediated cleavage of phosphatidylserine receptor on phagocytes and may contribute to ongoing airway inflammation. (+info)

Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo. (8/332)

Lipoxins (LX) are eicosanoids with antiinflammatory activity in glomerulonephritis (GN) and inflammatory diseases, hypersensitivity, and ischemia reperfusion injury. It has been demonstrated that LXA(4) stimulates non-phlogistic phagocytosis of apoptotic polymorphonuclear neutrophils (PMN) by monocyte-derived macrophages (Mphi) in vitro, suggesting a role for LX as endogenous pro-resolution lipid mediators. It is here reported that LXA(4), LXB(4), the aspirin-triggered LX (ATL) epimer, 15-epi-LXB(4), and a stable synthetic analogue 15(R/S)-methyl-LXA(4) stimulate phagocytosis of exogenously administered excess apoptotic PMN by macrophages (M phi) in vivo in a classic model of acute inflammation, namely thioglycollate-induced peritonitis. Significant enhancement of phagocytosis in vivo was observed with 15-min exposure to LX and with intraperitoneal doses of LXA(4), LXB(4), 15(R/S)-methyl-LXA(4), and 15-epi-LXB(4) of 2.5 to 10 micro g/kg. Non-phlogistic LX-stimulated phagocytosis by M phi was sensitive to inhibition of PKC and PI 3-kinase and associated with increased production of transforming growth factor-beta(1) (TGF-beta(1)). LX-stimulated phagocytosis was not inhibited by phosphatidylserine receptor (PSR) antisera and was abolished by prior exposure of M phi to beta 1,3-glucan, suggesting a novel M phi-PMN recognition mechanism. Interestingly, the recently described peptide agonists of the LXA(4) receptor (MYFINITL and LESIFRSLLFRVM) stimulated phagocytosis through a process associated with increased TGF-beta(1) release. These data provide the first demonstration that LXA(4), LXB(4), ATL, and LX stable analogues rapidly promote M phi phagocytosis of PMN in vivo and support a role for LX as rapidly acting, pro-resolution signals in inflammation. Engagement of the LXR by LX generated during cell-cell interactions in inflammation and by endogenous LXR peptide agonists released from distressed cells may be an important stimulus for clearance of apoptotic cells and may be amenable to pharmacologic mimicry for therapeutic gain. (+info)

Jumonji domain-containing histone demethylases (JHDMs) are a family of enzymes that are responsible for removing methyl groups from specific residues on histone proteins. These enzymes play crucial roles in the regulation of gene expression by modifying the chromatin structure and influencing the accessibility of transcription factors to DNA.

JHDMs contain a conserved Jumonji C (JmjC) domain, which is responsible for their demethylase activity. They are classified into two main groups based on the type of methyl group they remove: lysine-specific demethylases (KDMs) and arginine-specific demethylases (RDMs).

KDMs can be further divided into several subfamilies, including KDM2/7, KDM3, KDM4, KDM5, and KDM6, based on their substrate specificity and the number of methyl groups they remove. For example, KDM4 enzymes specifically demethylate di- and tri-methylated lysine 9 and lysine 36 residues on histone H3, while KDM5 enzymes target mono-, di-, and tri-methylated lysine 4 residues on histone H3.

RDMs, on the other hand, are responsible for demethylating arginine residues on histones, including symmetrically or asymmetrically dimethylated arginine 2, 8, 17, and 26 residues on histone H3 and H4.

Dysregulation of JHDMs has been implicated in various human diseases, including cancer, neurological disorders, and cardiovascular diseases. Therefore, understanding the functions and regulation of JHDMs is essential for developing novel therapeutic strategies to treat these diseases.

Histone demethylases are enzymes that remove methyl groups from histone proteins, which are the structural components around which DNA is wound in chromosomes. These enzymes play a crucial role in regulating gene expression by modifying the chromatin structure and influencing the accessibility of DNA to transcription factors and other regulatory proteins.

Histones can be methylated at various residues, including lysine and arginine residues, and different histone demethylases specifically target these modified residues. Histone demethylases are classified into two main categories based on their mechanisms of action:

1. Lysine-specific demethylases (LSDs): These enzymes belong to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family and specifically remove methyl groups from lysine residues. They target mono- and di-methylated lysines but cannot act on tri-methylated lysines.
2. Jumonji C (JmjC) domain-containing histone demethylases: These enzymes utilize Fe(II) and α-ketoglutarate as cofactors to hydroxylate methyl groups on lysine residues, leading to their removal. JmjC domain-containing histone demethylases can target all three states of lysine methylation (mono-, di-, and tri-methylated).

Dysregulation of histone demethylases has been implicated in various human diseases, including cancer, neurological disorders, and cardiovascular diseases. Therefore, understanding the functions and regulation of these enzymes is essential for developing novel therapeutic strategies to target these conditions.

Oxidoreductases are a class of enzymes that catalyze oxidation-reduction reactions, where a electron is transferred from one molecule to another. N-Demethylating oxidoreductases are a specific subclass of these enzymes that catalyze the removal of a methyl group (-CH3) from a nitrogen atom (-N) in a molecule, which is typically a xenobiotic compound (a foreign chemical substance found within an living organism). This process often involves the transfer of electrons and the formation of water as a byproduct.

The reaction catalyzed by N-demethylating oxidoreductases can be represented as follows:
R-N-CH3 + O2 + H2O → R-N-H + CH3OH + H2O2

where R represents the rest of the molecule. The removal of the methyl group is often an important step in the metabolism and detoxification of xenobiotic compounds, as it can make them more water soluble and facilitate their excretion from the body.

Histones are highly alkaline proteins found in the chromatin of eukaryotic cells. They are rich in basic amino acid residues, such as arginine and lysine, which give them their positive charge. Histones play a crucial role in packaging DNA into a more compact structure within the nucleus by forming a complex with it called a nucleosome. Each nucleosome contains about 146 base pairs of DNA wrapped around an octamer of eight histone proteins (two each of H2A, H2B, H3, and H4). The N-terminal tails of these histones are subject to various post-translational modifications, such as methylation, acetylation, and phosphorylation, which can influence chromatin structure and gene expression. Histone variants also exist, which can contribute to the regulation of specific genes and other nuclear processes.

Methylation, in the context of genetics and epigenetics, refers to the addition of a methyl group (CH3) to a molecule, usually to the nitrogenous base of DNA or to the side chain of amino acids in proteins. In DNA methylation, this process typically occurs at the 5-carbon position of cytosine residues that precede guanine residues (CpG sites) and is catalyzed by enzymes called DNA methyltransferases (DNMTs).

DNA methylation plays a crucial role in regulating gene expression, genomic imprinting, X-chromosome inactivation, and suppression of repetitive elements. Hypermethylation or hypomethylation of specific genes can lead to altered gene expression patterns, which have been associated with various human diseases, including cancer.

In summary, methylation is a fundamental epigenetic modification that influences genomic stability, gene regulation, and cellular function by introducing methyl groups to DNA or proteins.

Histone-Lysine N-Methyltransferase is a type of enzyme that transfers methyl groups to specific lysine residues on histone proteins. These histone proteins are the main protein components of chromatin, which is the complex of DNA and proteins that make up chromosomes.

Histone-Lysine N-Methyltransferases play a crucial role in the regulation of gene expression by modifying the structure of chromatin. The addition of methyl groups to histones can result in either the activation or repression of gene transcription, depending on the specific location and number of methyl groups added.

These enzymes are important targets for drug development, as their dysregulation has been implicated in various diseases, including cancer. Inhibitors of Histone-Lysine N-Methyltransferases have shown promise in preclinical studies for the treatment of certain types of cancer.

Lysine is an essential amino acid, which means that it cannot be synthesized by the human body and must be obtained through the diet. Its chemical formula is (2S)-2,6-diaminohexanoic acid. Lysine is necessary for the growth and maintenance of tissues in the body, and it plays a crucial role in the production of enzymes, hormones, and antibodies. It is also essential for the absorption of calcium and the formation of collagen, which is an important component of bones and connective tissue. Foods that are good sources of lysine include meat, poultry, fish, eggs, and dairy products.

Epigenetics is the study of heritable changes in gene function that occur without a change in the underlying DNA sequence. These changes can be caused by various mechanisms such as DNA methylation, histone modification, and non-coding RNA molecules. Epigenetic changes can be influenced by various factors including age, environment, lifestyle, and disease state.

Genetic epigenesis specifically refers to the study of how genetic factors influence these epigenetic modifications. Genetic variations between individuals can lead to differences in epigenetic patterns, which in turn can contribute to phenotypic variation and susceptibility to diseases. For example, certain genetic variants may predispose an individual to develop cancer, and environmental factors such as smoking or exposure to chemicals can interact with these genetic variants to trigger epigenetic changes that promote tumor growth.

Overall, the field of genetic epigenesis aims to understand how genetic and environmental factors interact to regulate gene expression and contribute to disease susceptibility.

Retinoblastoma-Binding Protein 2 (RBP2) is a protein that is encoded by the EZH2 gene in humans. It is a core component of the Polycomb Repressive Complex 2 (PRC2), which is a multi-subunit protein complex involved in the epigenetic regulation of gene expression through histone modification. Specifically, RBP2/EZH2 functions as a histone methyltransferase that trimethylates lysine 27 on histone H3 (H3K27me3), leading to transcriptional repression of target genes. Retinoblastoma-Binding Protein 2 was so named because it was initially identified as a protein that interacts with the retinoblastoma protein (pRb), a tumor suppressor that regulates cell cycle progression and differentiation. However, its role in the development of retinoblastoma or other cancers is not well understood.

Polycomb Repressive Complex 2 (PRC2) is a multi-protein complex that plays a crucial role in the epigenetic regulation of gene expression, primarily through the modification of histone proteins. It is named after the Polycomb group genes that were initially identified in Drosophila melanogaster (fruit flies) due to their involvement in maintaining the repressed state of homeotic genes during development.

The core components of PRC2 include:

1. Enhancer of Zeste Homolog 2 (EZH2) or its paralog EZH1: These are histone methyltransferases that catalyze the addition of methyl groups to lysine 27 on histone H3 (H3K27). The trimethylation of this residue (H3K27me3) is a hallmark of PRC2-mediated repression.
2. Suppressor of Zeste 12 (SUZ12): This protein is essential for the stability and methyltransferase activity of the complex.
3. Embryonic Ectoderm Development (EED): This protein recognizes and binds to the H3K27me3 mark, enhancing the methyltransferase activity of EZH2/EZH1 and promoting the spreading of the repressive mark along chromatin.
4. Retinoblastoma-associated Protein 46/48 (RbAP46/48): These are histone binding proteins that facilitate the interaction between PRC2 and nucleosomes, thereby contributing to the specificity of its targeting.

PRC2 is involved in various cellular processes, such as differentiation, proliferation, and development, by modulating the expression of genes critical for these functions. Dysregulation of PRC2 has been implicated in several human diseases, including cancers, where it often exhibits aberrant activity or mislocalization, leading to altered gene expression profiles.

Histone deacetylases (HDACs) are a group of enzymes that play a crucial role in the regulation of gene expression. They work by removing acetyl groups from histone proteins, which are the structural components around which DNA is wound to form chromatin, the material that makes up chromosomes.

Histone acetylation is a modification that generally results in an "open" chromatin structure, allowing for the transcription of genes into proteins. When HDACs remove these acetyl groups, the chromatin becomes more compact and gene expression is reduced or silenced.

HDACs are involved in various cellular processes, including development, differentiation, and survival. Dysregulation of HDAC activity has been implicated in several diseases, such as cancer, neurodegenerative disorders, and cardiovascular diseases. As a result, HDAC inhibitors have emerged as promising therapeutic agents for these conditions.

Histone Deacetylase Inhibitors (HDACIs) are a class of pharmaceutical compounds that inhibit the function of histone deacetylases (HDACs), enzymes that remove acetyl groups from histone proteins. Histones are alkaline proteins around which DNA is wound to form chromatin, the structure of which can be modified by the addition or removal of acetyl groups.

Histone acetylation generally results in a more "open" chromatin structure, making genes more accessible for transcription and leading to increased gene expression. Conversely, histone deacetylation typically results in a more "closed" chromatin structure, which can suppress gene expression. HDACIs block the activity of HDACs, resulting in an accumulation of acetylated histones and other proteins, and ultimately leading to changes in gene expression profiles.

HDACIs have been shown to exhibit anticancer properties by modulating the expression of genes involved in cell cycle regulation, apoptosis, and angiogenesis. As a result, HDACIs are being investigated as potential therapeutic agents for various types of cancer, including hematological malignancies and solid tumors. Some HDACIs have already been approved by regulatory authorities for the treatment of specific cancers, while others are still in clinical trials or preclinical development.

Chromatin is the complex of DNA, RNA, and proteins that make up the chromosomes in the nucleus of a cell. It is responsible for packaging the long DNA molecules into a more compact form that fits within the nucleus. Chromatin is made up of repeating units called nucleosomes, which consist of a histone protein octamer wrapped tightly by DNA. The structure of chromatin can be altered through chemical modifications to the histone proteins and DNA, which can influence gene expression and other cellular processes.

Histone Acetyltransferases (HATs) are a group of enzymes that play a crucial role in the regulation of gene expression. They function by adding acetyl groups to specific lysine residues on the N-terminal tails of histone proteins, which make up the structural core of nucleosomes - the fundamental units of chromatin.

The process of histone acetylation neutralizes the positive charge of lysine residues, reducing their attraction to the negatively charged DNA backbone. This leads to a more open and relaxed chromatin structure, facilitating the access of transcription factors and other regulatory proteins to the DNA, thereby promoting gene transcription.

HATs are classified into two main categories: type A HATs, which are primarily found in the nucleus and associated with transcriptional activation, and type B HATs, which are located in the cytoplasm and participate in chromatin assembly during DNA replication and repair. Dysregulation of HAT activity has been implicated in various human diseases, including cancer, neurodevelopmental disorders, and cardiovascular diseases.

Acetylation is a chemical process that involves the addition of an acetyl group (-COCH3) to a molecule. In the context of medical biochemistry, acetylation often refers to the post-translational modification of proteins, where an acetyl group is added to the amino group of a lysine residue in a protein by an enzyme called acetyltransferase. This modification can alter the function or stability of the protein and plays a crucial role in regulating various cellular processes such as gene expression, DNA repair, and cell signaling. Acetylation can also occur on other types of molecules, including lipids and carbohydrates, and has important implications for drug metabolism and toxicity.

"Entrez Gene: Jumonji domain containing 1C". Grupe A, Li Y, Rowland C, Nowotny P, Hinrichs AL, Smemo S, et al. (2006). "A scan ... Jmjd1C encodes a histone H3K9 demethylase. In addition, the JMJD1c gene has a role in mouse spermatogenesis. In male homozygous ... Jumonji domain containing 1C is a protein that in humans is encoded by the JMJD1C gene. The protein encoded by this gene ... interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to ...

https://en.wikipedia.org/wiki/JMJD1C

This domain has been demonstrated to bind to the histone tail and causes the methylation of the histone. Differing histone ... Histones H3 and H4 can also be manipulated through demethylation using histone lysine demethylase (KDM). This recently ... identified enzyme has a catalytically active site called the Jumonji domain (JmjC). The demethylation occurs when JmjC utilizes ... Although histone modifications occur throughout the entire sequence, the unstructured N-termini of histones (called histone ...

https://en.wikipedia.org/wiki/Epigenetics

... was found to be an H3K4 histone demethylase that binds to c-Myc. It was recently renamed to Lysine Demethylase 5 (KDM5). ... "Entrez Gene: JARID1A jumonji, AT rich interactive domain 1A". Secombe J, Li L, Carlos L, Eisenman RN (Mar 2007). "The Trithorax ... DiTacchio L, Le HD, Vollmers C, Hatori M, Witcher M, Secombe J, Panda S (2011). "Histone lysine demethylase JARID1a activates ... Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene. The protein encoded by this gene is a ...

https://en.wikipedia.org/wiki/KDM5A

Evening-phased transcription factor CCA1 Hiking Expedition (CHE) and histone demethylase jumonji C domain-containing 5 (JMJD5) ... reduced noise and temperature compensation in order to better understand circadian rhythms that can be found in every domain of ...

https://en.wikipedia.org/wiki/Repressilator

Zou MR, Cao J, Liu Z, Huh SJ, Polyak K, Yan Q (June 2014). "Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B ... Lysine-specific demethylase 5B also known as histone demethylase JARID1B is a demethylase enzyme that in humans is encoded by ... "Entrez Gene: JARID1B jumonji, AT rich interactive domain 1B". Kristensen LH, Nielsen AL, Helgstrand C, Lees M, Cloos P, Kastrup ... The whole Jarid1 family is a protein family that possesses H3K4 histone demethylase activity. Jarid1B has been implicated in ...

https://en.wikipedia.org/wiki/JARID1B

A small molecule inhibitor (GSK-J1) has been developed to inhibit the jumonji domain of KDM6 histone demethylase family to ... October 2007). "UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development". Nature. 449 ( ... August 2012). "A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response". Nature. 488 ... Lysine demethylase 6B is a protein that in humans is encoded by the KDM6B gene. KDM6B was found to be expressional increased ...

https://en.wikipedia.org/wiki/KDM6B

She has studied Jumonji domain-containing histone-lysine demethylases, complex proteins which catalyze the removal of ... methylation marks on the lysine residues of multiple histones can contain chromatin reader domains. These reader domains ... To probe the cellular function of the Jumonji family, the Galonić Fujimori laboratory develop small molecule inhibitors. She ...

https://en.wikipedia.org/wiki/Danica_Galonić_Fujimori

This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein with one JmjC domain, one JmjN domain, two ... "Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases". Cell. 125 (3): 467-81. doi:10.1016/j. ... "Entrez Gene: JMJD2C jumonji domain containing 2C". Boeckel, Jes-Niels; Derlet, Anja; Glaser, Simone F.; Luczak, Annika; Lucas, ... It functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated ...

https://en.wikipedia.org/wiki/KDM4C

... an enzyme encoded by the JARID2 gene Jumonji C (JmJC) domain-containing demethylases, the largest group of histone demethylases ... a railway station in Jumonji, Japan Jumonji University, Jumonji, Japan Jumanji (picture book), a 1981 fantasy children's ... Jūmonji (十文字) may refer to: Bishin Jumonji, Japanese photographer Chisako Jumonji, Japanese professional wrestler Sachiko ... Jumonji, Japanese professional wrestler Jūmonji Tomokazu, Japanese sumo wrestler Takanobu Jumonji, Japanese cyclist Jūmonji, ...

https://en.wikipedia.org/wiki/Jūmonji

Jumonji-C domains containing the active catalytic site of KDM2 through KDM8 Jumonji-N domains responsible for Jumonji-C domain ... Histone lysine demethylases possess a variety of domains that are responsible for histone recognition, DNA binding, methylated ... domains responsible for histone recognition and binding Histone lysine demethylases are classified according to their domains ... Mosammaparast N, Shi Y (2010). "Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases ...

https://en.wikipedia.org/wiki/Demethylase

This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein with a JmjN domain, a JmjC domain, a JD2H ... It functions as a trimethylation-specific demethylase, converting specific trimethylated histone on histone H3 lysine 9 and 36 ... "Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases". Cell. 125 (3): 467-81. doi:10.1016/j. ... "Entrez Gene: JMJD2A jumonji domain containing 2A". Black JC, Manning AL, Van Rechem C, Kim J, Ladd B, Cho J, Pineda CM, Murphy ...

https://en.wikipedia.org/wiki/KDM4A

JMJD6, a Jumonji domain-containing protein, was reported to demethylate H3R2me2. H3R2me2 is a major mark deposited by PRMT6. ... It is thought that a histone code dictates the expression of genes by a complex interaction between the histones in a ... The existence of arginine demethylases that could reverse arginine methylation is controversial. The name of this modification ... Histone methylation Histone methyltransferase Blanc, Roméo S.; Richard, Stéphane (2017). "Arginine Methylation: The Coming of ...

https://en.wikipedia.org/wiki/H3R2me2

JMJD6, a Jumonji domain-containing protein, was reported to demethylate H4R3me2. H4R3me2 is a major mark deposited by Prmt5. ... It is thought that a histone code dictates the expression of genes by a complex interaction between the histones in a ... The existence of arginine demethylases that could reverse arginine methylation is controversial. The name of this modification ... Histone methylation Histone methyltransferase Blanc, Roméo S.; Richard, Stéphane (2017). "Arginine Methylation: The Coming of ...

https://en.wikipedia.org/wiki/H4R3me2

"Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases". Cell. 125 (3): 467-81. doi:10.1016/j. ... "Entrez Gene: JMJD2D jumonji domain containing 2D". Liu Z, Cai Y, Wang Y, Nie Y, Zhang C, Xu Y, Zhang X, Lu Y, Wang Z, Poo M, ... Shin S, Janknecht R (August 2007). "Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D". Biochemical and ... Liu X, Wang Y, Gao Y, Su J, Zhang J, Xing X, Zhou C, Yao K, An Q, Zhang Y (February 2018). "H3K9 demethylase KDM4E is an ...

https://en.wikipedia.org/wiki/KDM4D

"Entrez Gene: JMJD6 jumonji domain containing 6". Boeckel JN, Guarani V, Koyanagi M, Roexe T, Lengeling A, Schermuly RT, Gellert ... They are predicted to function as protein hydroxylases or histone demethylases. This protein was first identified as a putative ... Chang B, Chen Y, Zhao Y, Bruick RK (October 2007). "JMJD6 is a histone arginine demethylase". Science. 318 (5849): 444-7. ... Klose RJ, Kallin EM, Zhang Y (September 2006). "JmjC-domain-containing proteins and histone demethylation". Nature Reviews ...

https://en.wikipedia.org/wiki/JMJD6

This gene encodes a zinc finger protein that contains a jumonji C (JmjC) domain and may play a role in hormone-dependent ... "Hypoxia upregulates the histone demethylase JMJD1A via HIF-1". Biochemical and Biophysical Research Communications. 372 (4): ... "Entrez Gene: Lysine demethylase 3A". Yamane K, Toumazou C, Tsukada Y, Erdjument-Bromage H, Tempst P, Wong J, Zhang Y (May 2006 ... This article incorporates text from the United States National Library of Medicine, which is in the public domain. v t e ( ...

https://en.wikipedia.org/wiki/KDM3A

2006). "Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases". Cell. 125 (3): 467-81. doi: ... "Entrez Gene: JMJD2B jumonji domain containing 2B". Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of ... Lysine-specific demethylase 4B is an enzyme that in humans is encoded by the KDM4B gene. KDM4B belongs to the alpha- ... 2005). "Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein". J. Biol. Chem. 280 ( ...

https://en.wikipedia.org/wiki/KDM4B

"Pan-Histone Demethylase Inhibitors Simultaneously Targeting Jumonji C and Lysine-Specific Demethylases Display High Anticancer ... the ankyrin repeat domain. A current focus of the group is modification of histones, in particular oxygenase catalysed N- ... The histone demethylases are of interest both with respect to their links to diseases, including cancer and inflammatory ... "Targeting histone lysine demethylases - Progress, challenges, and the future". Biochimica et Biophysica Acta (BBA) - Gene ...

https://en.wikipedia.org/wiki/Christopher_J._Schofield

"Entrez Gene: JARID1C jumonji, AT rich interactive domain 1C". Agate RJ, Choe M, Arnold AP (Feb 2004). "Sex differences in ... Tahiliani M, Mei P, Fang R, Leonor T, Rutenberg M, Shimizu F, Li J, Rao A, Shi Y (May 2007). "The histone H3K4 demethylase SMCX ... This gene is a member of the SMCY homolog family and encodes a protein with one ARID domain, one JmjC domain, one JmjN domain ... "The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases". Cell. 128 (6): 1077-88 ...

https://en.wikipedia.org/wiki/KDM5C

"Entrez Gene: JARID1D jumonji, AT rich interactive domain 1D". Simpson E, Scott D, Chandler P (1997). "The male-specific ... "The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases". Cell. 128 (6): 1077-88 ... Lysine-specific demethylase 5D is an enzyme that in humans is encoded by the KDM5D gene. KDM5D belongs to the alpha- ... This gene encodes a protein containing zinc finger domains. A short peptide derived from this protein is a minor ...

https://en.wikipedia.org/wiki/KDM5D

α-Ketoglutarate has been shown to be a cofactor for demethylases that contain the Jumonji C (JmjC) domain. α-Ketoglutarate can ... "Histone demethylation by a family of JmjC domain-containing proteins". Nature. 439 (7078): 811-816. doi:10.1038/nature04433. ... a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor". Cell. 125 (3): 483-495. doi: ...

https://en.wikipedia.org/wiki/Α-Ketoglutaric_acid

Our results show that many of these genes are regulated by hypoxia and define two groups of histone demethylases as new classes ... Patterns of induction were consistent across a range of cell lines with JMJD1A (where JMJD is Jumonji-domain containing) and ... Given the importance of histone methylation status in defining patterns of gene expression under different physiological and ... Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1alpha. ...

https://www.immunology.ox.ac.uk/publications/4796?a9687fb0-59d3-11ee-8986-061b866677b4

Inhibition of jumonji C domain containing histone demethylases in acute myeloid leukemia. ...

https://gcris.iyte.edu.tr/handle/11147/10126?mode=simple

Here, we report the characterization of a small-molecule inhibitor of Jumonji C domain-containing histone demethylases. The ... Its methyl ester prodrug, methylstat, selectively inhibits Jumonji C domain-containing his-tone demethylases in cells and may ... Histone demethylases are the most recent family of histone-modifying enzymes discovered. ... Histone methylations are important chromatin marks that regulate gene expression, genomic stability, DNA repair, and genomic ...

https://www.kennedy.ox.ac.uk/publications/141818

Jumonji Domain-Containing Histone Demethylases / deficiency* * Jumonji Domain-Containing Histone Demethylases / genetics ...

https://pubmed.ncbi.nlm.nih.gov/24100015/

https://en.wikipedia.org/wiki/JMJD1C

JmjC domain-containing histone demethylation protein 1A antibody. *Jumonji C domain containing histone demethylase 1A antibody ... Histone demethylase that specifically demethylates Lys-36 of histone H3, thereby playing a central role in histone code. ... Belongs to the JHDM1 histone demethylase family.. Contains 1 CXXC-type zinc finger.. Contains 1 F-box domain.. Contains 1 JmjC ... Xiong X et al. Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development ...

https://www.abcam.com/products/primary-antibodies/kdm2a-antibody-epr18602-ab191387.html?productwalltab=abreviews

Synonyms: Histone demethylase JARID1A, JARID1A, Jumonji/ARID domain-containing protein 1A, Lysine-specific demethylase 5A, RBBP ... JmjC: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2beta. Clissold, P.M., Ponting, C.P. Trends ... Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein. Gray, S.G., Iglesias, A.H., ...

https://www.wikigenes.org/e/gene/e/5927.html

Jumonji C domain-containing histone demethylases (JMJs) dynamically control the level of histone methylations. However, how JMJ ... This report reveals a new domain that exists only in plant PLA1s and suggests that the domain is essential for homodimerization ... the core-NAS domain is fused to a variable C-terminal domain. Compared to fungal and moss NAS that comprise merely a core-NAS ... inhibiting histone demethylation. Thus, our results uncover a regulatory mechanism for histone demethylations by JMJs. ...

https://pesquisa.bvsalud.org/portal/?lang=pt&q=mh:%22Arabidopsis/enzimologia%22

... and Jumonji C (JmjC)-domain-containing histone demethylases (131). ... Functionally the S protein has a receptor-binding subunit (S1), an S2 fusion domain (S2), separated by a cleavage site (S1/S2) ... The orf8 protein from SARS-CoV2 has no known functional domain or motif and is different from the orf8 or orf8b of SARS-CoV, ... 8 in the heptad repeat domain, 6 in the RBD, and 4 in the S1 subunit, modifying two peptides which are antigens for SARS-CoV ( ...

https://www.spandidos-publications.com/10.3892/ijmm.2020.4636

Histone demethylase JARID1C. *JARID1C. *JARID1Clysine-specific demethylase 5C. *Jumonji, AT rich interactive domain 1C (RBP2- ... This gene is a member of the SMCY homolog family and encodes a protein with one ARID domain, one JmjC domain, one JmjN domain ... of human Jumonji, AT rich interactive domain 1C using the numbering given in entry NP_004178.2 (GeneID 8242). ... Jumonji Inhibitors Overcome Radioresistance in Cancer through Changes in H3k4 Methylation at Double-Strand Breaks. Cell Rep. ...

https://www.novusbio.com/products/smcx-antibody_nb100-55328

... and jumonji C domain-containing histone lysine demethylases (JMJD3). Dicarboxylate carriers (DIC) and voltage-dependent anion ... Xiao M, Yang H, Xu W. Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are ... succinate has been known to pro mote deoxyribonucleic acid methylation through inhibition of histone demethylases and the ten- ... Xie Z, Dai J, Dai L. Lysine Succinylation and Lysine Malonylation in Histones. Mol Cell Proteomics. 2012; 11(5):100-107. PubMed ...

https://haematologica.org/article/view/8615

We show here that structurally distinct H3K9-active demethylases-the lysine-specific demethylase-1 (LSD1) and several Jumonji C ... A three-domain Cdt1 configuration embraces Mcm2, Mcm4, and Mcm6, nearly half of the hexamer. The Cdt1 C-terminal domain extends ... silencing of proliferation-related genes due to decoration of their promoters with repressive trimethylated histone H3 lysine 9 ... Cdc6 binding rearranges a short α-helix in the Orc1 AAA+ domain and the Orc2 WHD, leading to the activation of the Cdc6 ATPase ...

https://www.imperial.ac.uk/people/chris.speck/publications.html

Jarid2 contains a Jumonji C domain, but is devoid of detectable histone demethylase activity. Instead, its artificial ... Jumonji, AT rich interactive domain 2: Biological Overview , References Gene name - Jumonji, AT rich interactive domain 2 ... Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila. Sci Rep 7(1): 5240. PubMed ID: ... Jumonji (JmjC) domain proteins (see Jarid2) influence gene expression and chromatin organization by way of histone ...

https://www.sdbonline.org/sites/fly/genebrief/jarid2.htm

... and jumonji domain containing 3 (JMJD3, also known as KDM6B), which specifically remove the repressive histone H3 lysine 27 ... A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 2012;488:404-8. ... The identification of selective small-molecule inhibitors of histone demethylases would provide insight into the activity and ... Impact: These structural insights provide a framework for future development of histone demethylase inhibitors. ...

https://aacrjournals.org/cancerdiscovery/article/2/9/764/3532/A-Selective-H3K27me3-Demethylase-Inhibitor-Blocks

... histone H3 Lys 9 demethylase, histone H3 lysine 9 demethylase, histone H3 lysine 9 Jumonji demethylase, histone H3 lysine 9 ... jmjC histone demethylase, JmjC-domain-containing histone demethylase 2A, JMJD1A, JMJD1B, JMJD2A, Jmjd2c histone demethylase, ... H3K9 demethylase, H3K9 histone demethylase, H3K9 Jumonji demethylase, H3K9 mono- and di-demethylase, H3K9Me2 demethylase, ... mono- and di-demethylase, histone H3K9 demethylase, histone lysine demethylase, IBM1, JHDM2A, JMJ25, JMJ27, JmjC domain- ...

https://brenda-enzymes.org/all_enzymes.php?ecno=1.14.11.65

Jumonji Domain Containing Histone Demethylases use Jumonji Domain-Containing Histone Demethylases Jumonji Domain Containing ... JmjC Domain Containing Histone Demethylases use Jumonji Domain-Containing Histone Demethylases JmjC Domain-Containing Histone ... Jumonji Domain-Containing Protein 1A use Retinoblastoma-Binding Protein 2 Jumonji, AT Rich Interactive Domain 1A use ... Jumonji Domain-Containing Histone Demethylases ... Demethylases use Jumonji Domain-Containing Histone Demethylases ...

https://decs.bvsalud.org/I/DeCS2020_Alfab-J.htm

To discover new inhibitors for the KDM4 demethylases, enzymes overexpressed in several cancers, we docked a library of 600,000 ... Development of tool molecules that inhibit Jumonji demethylases allows for the investigation of cancer-associated transcription ... Crystallography, X-Ray, Drug Design, Enzyme Inhibitors, Humans, Jumonji Domain-Containing Histone Demethylases, Mesalamine, ... Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors. Korczynska M., Le DD., Younger N., Gregori ...

https://www.immunology.ox.ac.uk/publications/584051