RBBP4 modulates gene activity through acetylation and methylation of histone H3 lysine 27 [ChIP-Seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE183292 | GEO | 2022/03/09
REPOSITORIES: GEO
Similar Datasets
Project description:RNAseq anaysis detected dramatic changes in transcriptome due to Rbbp4 disruption
2022-03-09 | GSE183291 | GEO
Project description:RBBP4 modulates gene activity through acetylation and methylation of histone H3 lysine 27
| PRJNA759890 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-03-09 | GSE183298 | GEO
Project description:RBBP4 modulates gene activity through acetylation and methylation of histone H3 lysine 27 [ChIP-Seq]
| PRJNA759893 | ENA
Project description:RBBP4 modulates gene activity through acetylation and methylation of histone H3 lysine 27 [RNA-Seq]
| PRJNA759892 | ENA
Project description:BackgroundHistone post-translational modifications (PTMs) play an important role in the regulation of the expression of genes, including those involved in cancer development and progression. However, our knowledge of PTM patterns in human tumours is limited.MethodsMS-based analyses were used to quantify global alterations of histone PTMs in colorectal cancer (CRC) samples. Histones isolated from 12 CRCs and their corresponding normal mucosa by acidic extraction were separated by SDS-PAGE and analysed by liquid chromatography-mass spectrometry.ResultsAmong 96 modified peptides, 41 distinct PTM sites were identified, of which 7, 13, 11, and 10 were located within the H2A, H2B, H3, and H4 sequences, respectively, and distributed among the amino-terminal tails and the globular domain of the four histones. Modification intensities were quantified for 33 sites, of which 4 showed significant (p-value ≤ 0.05) differences between CRC tissues and healthy mucosa samples. We identified histone H3 lysine 27 acetylation (H3K27Ac) as a modification upregulated in CRC, which had not been shown previously.ConclusionsThe present results indicate the usefulness of a bottom-up proteomic approach for the detection of histone modifications at a global scale. The differential abundance of H3K27Ac mark in CRC, a PTM associated with active enhancers, suggests its role in regulating genes whose expression changes in CRC.
| S-EPMC4071346 | biostudies-literature
Project description:Trimethylation of histone H3 lysine 27 (H3K27me3) by Polycomb repressive complex 2 (PRC2) is essential for transcriptional silencing of Polycomb target genes, whereas acetylation of H3K27 (H3K27ac) has recently been shown to be associated with many active mammalian genes. The Trithorax protein (TRX), which associates with the histone acetyltransferase CBP, is required for maintenance of transcriptionally active states and antagonizes Polycomb silencing, although the mechanism underlying this antagonism is unknown. Here we show that H3K27 is specifically acetylated by Drosophila CBP and its deacetylation involves RPD3. H3K27ac is present at high levels in early embryos and declines after 4 hours as H3K27me3 increases. Knockdown of E(Z) decreases H3K27me3 and increases H3K27ac in bulk histones and at the promoter of the repressed Polycomb target gene abd-A, suggesting that these indeed constitute alternative modifications at some H3K27 sites. Moderate overexpression of CBP in vivo causes a global increase in H3K27ac and a decrease in H3K27me3, and strongly enhances Polycomb mutant phenotypes. We also show that TRX is required for H3K27 acetylation. TRX overexpression also causes an increase in H3K27ac and a concomitant decrease in H3K27me3 and leads to defects in Polycomb silencing. Chromatin immunoprecipitation coupled with DNA microarray (ChIP-chip) analysis reveals that H3K27ac and H3K27me3 are mutually exclusive and that H3K27ac and H3K4me3 signals coincide at most sites. We propose that TRX-dependent acetylation of H3K27 by CBP prevents H3K27me3 at Polycomb target genes and constitutes a key part of the molecular mechanism by which TRX antagonizes or prevents Polycomb silencing.
| S-EPMC2730368 | biostudies-literature
Project description:Histone lysine acetylation and methylation regulate gene transcription through coordination of chromatin structure and transcriptional activity. However, our understanding of the role of histones in gene regulation is far from complete, in part due to newly discovered novel histone modifications, whose functions are yet to be uncovered1. Here we report that histone H3 lysine 27 crotonylation (H3K27cr) is selectively recognized by the YEATS domain of GAS41 in association with SIN3a-HDAC1/2 co-repressor complex for gene transcriptional repression. The GAS41 YEATS domain dimer binds proto-oncogenic transcription factor c-Myc, which recruits GAS41/SIN3a-HDAC1/2 complex to target gene loci in chromatin such as cell cycle inhibitor p21. Transcriptional de-repression of p21, directed by tumor suppressor p53 upon doxorubicin stimulation, entails dissociation of c-Myc/GAS41/SIN3a-HDAC1/2 complex from chromatin, reduced H3K27 crotonylation, and consequentially increased H3K27 acetylation at p21 locus. GAS41 knockout or H3K27cr binding depletion with CRISPR/Cas9 results in p21 activation, cell cycle arrest and tumor growth inhibition in mice. Our study explains mechanistically causal effect of GAS41 and c-Myc gene amplification on down-regulation of p21 in human colorectal cancer, and suggests GAS41 as an anti-cancer target. We propose that H3K27 crotonylation represents a previously unrecognized, distinct chromatin state for gene transcriptional repression in contrast to H3K27 trimethylation for long-term transcriptional silencing and H3K27 acetylation for transcriptional activation.
2023-10-03 | GSE128590 | GEO
Project description:BackgroundStunting is a condition in which a child does not reach their full growth potential due to chronic undernutrition. It arises during the first 2 years of a child's life and is associated with developmental deficiencies and life-long health problems. Current interventions provide some benefit, but new approaches to prevention and treatment grounded in a molecular understanding of stunting are needed. Epigenetic analyses are critical as they can provide insight into how signals from a poor environment lead to changes in cell function.ResultsHere we profiled histone H3 acetylation on lysine 27 (H3K27ac) in peripheral blood mononuclear cells (PBMCs) of 18-week-old (n = 14) and 1-year-old children (n = 22) living in an urban slum in Dhaka, Bangladesh. We show that 18-week-old children destined to become stunted have elevated levels of H3K27ac overall, functional analysis of which indicates activation of the immune system and stress response pathways as a primary response to a poor environment with high pathogen load. Conversely, overt stunting at 1-year-of age is associated with globally reduced H3K27ac that is indicative of metabolic rewiring and downregulation of the immune system and DNA repair pathways that are likely secondary responses to chronic exposure to a poor environment with limited nutrients. Among processes altered in 1-year-old children, we identified one-carbon metabolism, the significance of which is supported by integrative analysis with results from histone H3 trimethylation on lysine 4 (H3K4me3). Together, these results suggest altered one-carbon metabolism in this population of stunted children.ConclusionsThe epigenomes of stunted children undergo two global changes in H3K27ac within their first year of life, which are associated with probable initial hyperactive immune responses followed by reduced metabolic capacity. Limitation of one-carbon metabolites may play a key role in the development of stunting. Trial registration ClinicalTrials.gov NCT01375647. Registered 17 June 2011, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01375647 .
| S-EPMC8474848 | biostudies-literature
Project description:ETV6-RUNX1 is a fusion protein bringing together almost the entire coding sequence of RUNX1, including the DNA binding runt domain, and the N-terminus of ETV6 which is known to include transcriptional repressors including histone deacetylation 3 (HDAC3). Here we perform ChIP-seq for the active chromatin mark H3K27ac in the NALM6 B-cell acute lymphoblastic leukaemia cell line expressing ETV6-RUNX1 or mutant derivatives of ETV6-RUNX1: Delta helix-loop-helix (dHLH) is a deletion of the pointed domain; R139G is a point mutation in the runt DNA-binding domain.
2022-10-31 | E-MTAB-12207 | biostudies-arrayexpress