Chromatin remodelers in human cancers. Medical search. Frequent questions

Mutations in genes encoding BAF complex proteins occur in more than 20% of all human cancers and developmental diseases. (imb.de)
It helps to open up the chromatin by neutralizing the positive charge of histone lysine residues and providing binding platforms for "reader" proteins. (omicsdi.org)
It has therefore been proposed that the oncogenic activity of MLL-fusion proteins depends on chromatin targeting functions exerted by the MLL N-terminus in combination with other functional properties encoded by the fusion partners 6 . (nature.com)
Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler ɑ-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS's ability to promote PDAC. (ox.ac.uk)
To do so, they coupled findings from 238 DNA-protein-binding experiments performed by the ENCODE project - a massive, multiyear international effort to identify the functional elements of the human genome - with a laboratory-based technique to identify binding patterns among the proteins themselves. (pharmaceuticalintelligence.com)
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. (lookformedical.com)
DDX5 is required for cell proliferation by controlling the transcription of genes expressing DNA replication proteins in cancer cells in which the DDX5 locus is amplified, and this has uncovered a dependence on DDX5 for cell proliferation. (aacrjournals.org)
Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (bmj.com)
All living organisms package their DNA with chromatin proteins. (biologists.com)

My research focuses on one particular class of chromatin remodelers known as BAF complexes, which are very large multi-protein complexes containing many subunits. (imb.de)
In mammals, two chromatin remodeling complexes, Tip60/p400 and SRCAP, exchange the canonical histone H2A for H2A.Z in the chromatin. (omicsdi.org)
Here we show that Glioma Amplified Sequence 41 (Gas41), a shared subunit of the two H2A.Z-depositing complexes, functions as a reader of histone lysine acetylation and recruits Tip60/p400 and SRCAP to deposit H2A.Z into specific chromatin regions including bivalent domains. (omicsdi.org)
Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. (refine.bio)
The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling. (lookformedical.com)
Osei P, Northcote-Smith J, Fang J, Singh K, Ortu F, Suntharalingam K . The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Bi-nuclear Copper(II)-Phenanthroline Complexes. (le.ac.uk)
XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair. (uni-muenchen.de)
PTFs also enable other transcription factors, histone modifiers, and nucleosome remodeling complexes to alter the chromatin state and promote gene expression of silenced genes. (cytoskeleton.com)

ATP-dependent chromatin remodelers can modulate chromatin accessibility by moving or evicting nucleosomes. (imb.de)
The Mueller-Planitz lab studies the core components of chromatin - the nucleosomes and the machinery that places them in the genome. (tu-dresden.de)
Nucleosomes are crucial to human health. (tu-dresden.de)
Aging, for instance, disrupts the nucleosome landscape, destabilizing the genome, and mutations in nucleosomes are drivers of cancers. (tu-dresden.de)
Remodelers move, assemble, or eject nucleosomes in an ATP-dependent fashion. (tu-dresden.de)
These 'spacing remodelers' thereby generate arrays of nucleosomes with a surprising regularity, and these arrays are conserved throughout eukaryotes. (tu-dresden.de)
Intro Eukaryotic DNA-binding sites are often not accessible to their cognate factors because the sites lay within epigenetically silent chromatin and are occupied by nucleosomes. (irjs.info)
They bind to nucleosomes and convert the energy of ATP hydrolysis into the movement, restructuring, or ejection of histone octamers depending on the remodeler. (irjs.info)
ISWI slides nucleosomes along DNA, enabling the structural changes of chromatin required for the regulated use of eukaryotic genomes. (cipsm.de)

In eukaryotic nuclei, chromatin remodelers mediate the dynamics of nucleosome plans and participate in Ki16425 cost most DNA-dependent processes (L?ngst & Manelyte, 2015 for a recent overview). (irjs.info)
In this closed state, chromatin structure becomes an obstacle for eukaryotic transcription by impeding the interaction of RNA polymerase machinery and most transcription factors (TFs). (cytoskeleton.com)

4:00 PM March 8, 2022 - 'Why Don't We Get More Cancer: The critical role of extracellular matrix and microenvironment in malignancy and dormancy? (stanford.edu)

The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. (refine.bio)

The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. (cipsm.de)

Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting? (mdpi.com)
Although these responses are well studied at protein and transcriptional levels, the molecular underpinnings of chromatin dynamics in response to metabolic and inflammatory challenges in islets are largely unclear. (mayo.edu)
Our previous studies showed that the hypoxia-sensitive chromatin remodeler KAP1 was targeted by the KSHV-encoded latency-associated nuclear antigen (LANA) to repress expression of the major lytic replication and transcriptional activator (RTA). (unr.edu)
Transcriptional regulation of the human ferritin gene by coordinated regulation of Nrf2 and protein arginine methyltransferases PRMT1 and PRMT4. (embl.de)
PRMT6 is a protein arginine methyltransferase that has been implicated in transcriptional regulation, DNA repair, and human immunodeficiency virus pathogenesis. (embl.de)
Chromatin target of Prmt1 (Chtop) is a vertebrate-specific chromatin-bound protein that plays an important role in transcriptional regulation. (embl.de)
The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA. (lookformedical.com)

We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. (cipsm.de)
We hypothesize that CDCA7 becomes dispensable in species that lost HELLS or DNA methylation, and/or the loss of CDCA7 triggers the replacement of DNA methylation by other chromatin regulation mechanisms. (elifesciences.org)
Similarly, marked modifications occur in the larger phosphoprotein clusters involving cytoskeleton and neuronal structures, membrane stabilization, and kinase regulation in the late elderly.Present findings may increase understanding of human brain proteostasis modifications in the elderly in the subpopulation of individuals not having AD neuropathological change and any other neurodegenerative change in any telencephalon region. (ibecbarcelona.eu)

Schick S*, Fournier D*, Thakurela S, Sahu SK, Garding A and Tiwari VK (2015) Dynamics of chromatin accessibility and epigenetic state in response to UV damage . (imb.de)

We thus identify macrodomains as modules that directly sense PARP activation in vivo and establish macroH2A histones as dynamic regulators of chromatin plasticity. (nature.com)

Genomic DNA is highly compacted into chromatin in order to fit into the nucleus of a cell. (imb.de)

The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. (lookformedical.com)

ont permis la publication de plus de 370 articles et monographies, dont une 44 en 2020. (u-paris.fr)

Depletion of GAS41 or disruption of the interaction between its YEATS domain and acetylated histones impairs the association of histone variant H2A.Z with chromatin and consequently suppresses cancer cell growth and survival both in vitro and in vivo. (omicsdi.org)
Although initially discovered as a retinoblastoma binding protein it has an affinity for core HISTONES and is a subunit of chromatin assembly factor-1 and polycomb repressive complex 2. (lookformedical.com)
Pioneers conquer core histones at the chromatin frontier. (uni-muenchen.de)

Among immune cells, Foxp3 + regulatory T cells (Treg cells) are potent inhibitors of cancer immunity, and their presence within solid tumors is generally associated with a poor prognosis. (mdpi.com)
ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) analyses in lung cancer cells reveal that GAS41 colocalizes with H3K27ac and H3K14ac on the promoters of actively transcribed genes. (omicsdi.org)
Furthermore, TGF-ß1 secretion from cancer-associated fibroblasts increased MIR99AHG expression in CRC cells. (bvsalud.org)
Characterization of this SIRT6 allele (centSIRT6) demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double-strand break repair, and more robustly kill cancer cells compared with wild-type SIRT6. (bvsalud.org)
Dissemination of tumour cells and metastatic spread as well as cancer resistance to standard treatment are still the common cause of treatment failure and eventually death in prostate cancer patients. (uni-hamburg.de)
Metastatic outgrowth of disseminated tumor cells is thought to be fueled by clonal cooperation of tumor clones from early and late stages of cancer evolution. (uni-hamburg.de)
Circulating tumor cells (CTCs) can be detected in the peripheral blood and peritoneal liquid in most of the ovarian cancer patients in the different stages of the disease. (uni-hamburg.de)
This study will elucidate the metastatic cascade of ovarian cancer by investigating the natural cancer evolution through the analysis of single tumor cells on genomic, transcriptomic, proteomic, and methylomic (multi‐omic) level. (uni-hamburg.de)
The epigenome of dysfunctional beta cells is shaped by dysregulation of multiple chromatin regulators. (mayo.edu)
Using genomics, single-cell profiling, proteomics and mouse genetic models, Dr. Wei's group is exploring how microenvironment signals - sensed by nuclear hormone receptors and gated by the balance between permissive and repressive chromatin remodelers - transform the chromatin landscape and induce functional response in residential innate immune cells and pancreatic endocrine cells. (mayo.edu)
IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. (cipsm.de)
Breast and lung cancer cells of murine and human origin induced IL-22 production from memory CD4 + T cells. (cipsm.de)
Differential Expression of Multiple Disease-Related Protein Groups Induced by Valproic Acid in Human SH-SY5Y Neuroblastoma Cells. (anticorps-enligne.fr)
We applied an assay that measures the stability of maintenance of an episomal plasmid in human tissue culture cells to screen for new DNA replication factors. (aacrjournals.org)
We find that the DDX5 locus is frequently amplified in breast cancer and that breast cancer-derived cells with amplification of DDX5 are much more sensitive to its depletion than breast cancer cells and a breast epithelial cell line that lacks DDX5 amplification. (aacrjournals.org)
Given the high frequency of DDX5 amplification in breast cancer, our results highlight DDX5 as a promising candidate for targeted therapy of breast tumors with DDX5 amplification, and indeed we show that DDX5 inhibition sensitizes a subset of breast cancer cells to trastuzumab. (aacrjournals.org)
Understanding how DNA replication is regulated in human cells can provide insight into cancer development and may reveal vulnerabilities that can be exploited therapeutically. (aacrjournals.org)
Chemical conversion of human conventional Pluripotent Stem Cells to Trophoblast Stem Cells. (axonmedchem.com)
Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells. (axonmedchem.com)
Stability of Imprinting and Differentiation Capacity in Naïve Human Cells Induced by Chemical Inhibition of CDK8 and CDK19. (axonmedchem.com)
The catalytic activity of human Telomerase Reverse Transcriptase (TERT) compensates for the loss of telomere length, eroded during each cell cycle, to ensure a correct division of stem and germinal cells. (biomedcentral.com)

Here, we discovered that the long noncoding RNA (lncRNA) MIR99AHG regulated alternative splicing to alter the activity of a chromatin remodeler and promote metastatic behaviors in colorectal cancer (CRC). (bvsalud.org)
Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer. (atlasgeneticsoncology.org)

Notably, histone macroH2A1.1 senses PARP1 activation, transiently compacts chromatin, reduces the recruitment of DNA damage factor Ku70-Ku80 and alters γ-H2AX patterns, whereas the splice variant macroH2A1.2, which is deficient in poly-ADP-ribose binding, does not mediate chromatin rearrangements upon PARP1 activation. (nature.com)

Arsenic exposure of human HaCaT keratinocytes induced nuclear accumulation of PRMT1 and PRMT4, histone H4R3 and H3R17 methylation proximal to the ARE, but not to the non-ARE regions of ferritin genes. (embl.de)
At a very basic level, we are learning who likes to work with whom to regulate around 20,000 human genes," said Michael Snyder , PhD, professor and chair of genetics at Stanford. (pharmaceuticalintelligence.com)
BRCA1 and BRCA2 genes are considered susceptibility genes in hereditary breast cancer but are also involved in important metabolic functions of cell life. (oncotarget.com)
The transcription factors Oct4, Sox2, and Klf4 were found to trigger endogenous expression of pluripotent genes [2] and were identified as PTFs due to their ability to access closed chromatin [3] . (cytoskeleton.com)

The study provides new mechanistic evidence for a link between the cellular levels of Smarca5 and selected hallmarks of cancer that include genome instability, epigenetic reprogramming, evasion of cellular senescence, and cell immortality. (who.int)
Dr. Wei's laboratory is investigating the fundamental mechanisms of a novel hormone-induced epigenetic switch that mediates beta cell anti-inflammatory responses in diabetes and exploring the therapeutic potential of the synergistic modulation of hormone receptors and the chromatin environment in diabetes. (mayo.edu)
The comprehensive and integrated data sets such as epigenetic changes, including histone modification, chromatin accessibility and 3D long-range interactions, will establish the epigenetic landscape of beta cell dysfunction. (mayo.edu)

SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity. (axonmedchem.com)

Pan-cancer predictions of transcription factors mediating aberrant DNA methylation. (cnrs.fr)
This subset of transcription factors, known as pioneer transcription factors (PTFs), possess the ability to engage closed chromatin that is not accessible by other types of transcription factors, establish gene expression, and elicit cell reprogramming. (cytoskeleton.com)

A new study conducted by scientists at the International Agency for Research on Cancer (IARC), with partners from Charles University in Prague (Czechia), describes new roles of a key chromatin remodelling enzyme, Smarca5, which is often deregulated in human cancers. (who.int)
Our results confirmed the overexpression of miR-151-5p and, interestingly, its role in the targeting of SMARCA5, a chromatin remodeler. (oncotarget.com)

The histone chaperone ANP32B regulates chromatin incorporation of the atypical human histone variant macroH2A. (uni-muenchen.de)

ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. (ox.ac.uk)
Understanding factors required for DNA replication will enrich our knowledge of this important process and potentially identify vulnerabilities that can be exploited in cancer therapy. (aacrjournals.org)
Defects in the control of cell proliferation are a hallmark of cancer, and DNA replication is a key process for cell proliferation. (aacrjournals.org)

Here we show that preclinical models of synovial sarcoma - a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein - display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. (refine.bio)
Five friends of methylated chromatin target of protein-arginine-methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation to desumoylation. (embl.de)
A retinoblastoma-binding protein that is involved in CHROMATIN REMODELING, histone deacetylation, and repression of GENETIC TRANSCRIPTION. (lookformedical.com)
Disordered protein regions partner up the cBAF remodeler for a chromatin dance. (uni-muenchen.de)

We conclude that BZLF1 reactivates the EBV genome by directly binding to silenced chromatin and recruiting cellular chromatin-remodeling enzymes, which implement a permissive Ki16425 cost state for lytic viral transcription. (irjs.info)

By extending this analysis to study all major oncogenic pathways pan-cancer I now aim to identify whether oncogenic convergence is unique to B-ALL, or whether it represents a new hallmark of cancer that can be exploited to design personalized combination therapies. (yale.edu)
Elevated levels of replicative stress in gynecological cancers arising from uncontrolled oncogenic activation, loss of key tumor suppressors, and frequent defects in the DNA repair machinery are an intrinsic vulnerability for therapeutic exploitation. (bmj.com)

i) an early (hormone-sensitive, node-positive) (subproject 1) and also (ii) a late (metastatic castration-resistant) (subproject 2) stage of metastatic disease as a special exemplar, taking into account the complexity of advanced prostate cancer. (uni-hamburg.de)
Dissecting the metastatic cascade in ovarian cancer and understanding the evolutionary pathways of how and when metastasis takes place will greatly help in the management of cancer patients. (uni-hamburg.de)

To identify novel factors involved in maintaining islet endocrine cell function and survival in stressed conditions, the Wei lab is combining genome-wide CRISPR screening with 3D stem cell-differentiated human islet-like organoids to discover novel chromatin regulators in the mediation of cellular dysfunction and inflammatory response. (mayo.edu)
Cell invasion is a crucial step of tumor metastasis , finding new regulators of which offers potential drug targets for cancer therapy. (sdbonline.org)

Driven by the challenges his patients face when fighting cancer - specifically addressing the vast heterogeneity in treatment response by identifying the optimal treatment to pair with each patient's unique biology - he leads a laboratory focused on developing integrated circuits (or "computer chips") for in vivo cancer sensing. (nih.gov)
They aim to globally understand how the physical and chemical properties of materials affect interactions with biological systems in vitro and in vivo in the context of improving cancer and genetic disease therapies. (utsouthwestern.edu)

Poly-ADP-ribosylation is a post-translational modification catalyzed by PARP enzymes with roles in transcription and chromatin biology. (nature.com)
During my PhD at Cardiff University I developed novel bioinformatics methods to analyze nucleosome maps generated by MNase-digest sequencing in order to understand the roles of chromatin remodelers in controlling developmental expression programs through nucleosome positioning. (yale.edu)

Remodelers are classified according to their ATPase subunit into four major (SWI/SNF, ISWI, INO80, and CHD) and several minor families and further differentiated by their connected subunits. (irjs.info)

DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. (cipsm.de)

Long before the identification of its molecular nature, it was recognized that chromatin exists in two main states: the densely stained heterochromatin contrasting with euchromatin ( Heitz, 1928 ). (biologists.com)

Walker eventually left Texas A&M to become the director of the Center for Precision Environmental Health and a professor in the Departments of Molecular and Cellular Biology, Medicine, and Molecular and Human Genetics at Baylor College of Medicine. (wikipedia.org)
Elise Cai performed her dissertation research in the Molecular and Cellular Biology Program under the mentorship of Dr. Slobodan Beronja at the Fred Hutchinson Cancer Research Center. (washington.edu)
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)

Human pregnane X receptor (PXR) is a major nuclear receptor that upregulates the expression of drug-metabolizing enzymes such as CYP3A4. (aspetjournals.org)

Gera R, Mokbel L, Jiang WG, Mokbel K mRNA Expression of Cancer Genomics Proteomics. (cancerindex.org)
Our objective was to determine if CDK2AP1 mRNA expression levels were consistent with tumour-suppressive functions in breast cancer. (cancerindex.org)
To our knowledge, this is the first study in the literature to examine the mRNA expression of CDK2AP1 in human breast cancer over a long-term follow-up period. (cancerindex.org)
MIR99AHG bound to and stabilized the RNA splicing factor PTBP1, and this complex increased cassette exon inclusion in the mRNA encoding the chromatin remodeling gene SMARCA1. (bvsalud.org)

Both subprojects aim to identify distinct signatures within the genome, transcriptome, epigenome and/or kinome, which contribute to prostate cancer dissemination, metastasis and progression to castration resistant phenotype, which will assist in developing new biomarkers and novel, biomarker-driven, personalised therapeutic strategies (subproject 3). (uni-hamburg.de)

In my research, I use a combination of genomics, proteomics, molecular biology, screening and imaging approaches to dissect the functions of individual BAF subunits in cancer and developmental disease. (imb.de)
During dynamic developmental events, such as sexual reproduction, we propose that dramatic and rapid reconfiguration of source-sink relationships modifies chromatin states. (biologists.com)

In collaboration with Dr. Andrew Hsieh's lab at the Hutch, she discovered similar translational regulatory pathways involved in prostate cancer. (washington.edu)

This sensitivity appears only in female mice, mimicking a significant prevalence of ATRX mutations in human female PDAC patients. (ox.ac.uk)

Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent-the naked mole-rat1,2. (bvsalud.org)
The human being genome encodes 53 different remodeler ATPases (L?ngst & Manelyte, 2015), which are highly abundant chromatin factors with roughly one remodeling complex. (irjs.info)

A better understanding the biology of the above-mentioned features will indeed lead to more effective cancer therapy options in prostate cancer. (uni-hamburg.de)
The work should be of interest to colleagues in the fields of evolutionary biology, chromatin biology and genome biology. (elifesciences.org)

In conclusion, our data showed the possibility of considering the overexpression of PARP1 and miR-151-5p as biomarkers useful to correctly treat sporadic breast cancers, which eventually could be considered as BRCAness tumors, with PARP-inhibitors. (oncotarget.com)
The abnormal reactivation of human Telomerase Reverse Transcriptase (TERT) is a common hallmark of human solid tumors. (biomedcentral.com)

Moreover, the identification of fork protection as a key mechanism of resistance to chemo- and poly (ADP-ribose) polymerase inhibitor therapy in ovarian cancer further increases the priority that should be accorded to the development of strategies targeting replicative stress. (bmj.com)

Alternative splicing regulates gene expression and functional diversity and is often dysregulated in human cancers. (bvsalud.org)

Recruitment of 53BP1 to chromatin flanking double strand breaks (DSBs) requires γH2AX/MDC1/RNF8-dependent ubiquitination of chromatin and interaction of 53BP1 with histone H4 methylated on lysine 20 (H4K20me). (cipsm.de)

In this review, we summarize the current knowledge on the different intracellular pathways involved in the programming of Treg cell homeostasis and functions in cancer. (mdpi.com)
How mutant IDH and 2-HG alter signaling pathways to promote cancer, though, remains unclear. (refine.bio)

Long non-coding RNA (lncRNA) H19 in human cancer: From proliferation and metastasis to therapy. (atlasgeneticsoncology.org)

In particular, they are focused on the development of new materials that can deliver genetic medicines to treat cancer and genetic diseases. (utsouthwestern.edu)

Closed chromatin" in this context is defined by a lack DNase hypersensitivity and indeterminate histone modification pattern. (cytoskeleton.com)

Genomics offers new tools to understanding the underlying genetic alterations that lead to genomic instability and, ultimately, to developing better treatments for cancers. (dpetiquetas.com.br)

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