Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dynamic competing histone H4 K5K8 acetylation and butyrylation are hallmarks of highly active gene promoters

ABSTRACT: Newly discovered histone lysine acylations increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters, where acetylation guides the binding of Brdt, a bromodomain-and-extra-terminal protein, thereby mediating stage-specific gene expression programs. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbour competing histone acetylation and butyrylation marks at H4 K5 and K8. Histone butyrylation, despite acting as a direct stimulator of transcription, competes with acetylation, especially at H4 K5, to prevent Brdt binding. The observed in vivo H4 K5K8 acetylation butyrylation state at active promoters is reproduced in vitro where p300 indistinctly acetylates and butyrylates H4 K5 and K8. Altogether, highly active gene promoter regions are characterized by alternating H4 acetylation and butyrylation sustaining direct gene activation and a dynamic bromodomain binding.

ORGANISM(S): Mus musculus

PROVIDER: GSE77277 | GEO | 2016/07/13

SECONDARY ACCESSION(S): PRJNA309951

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nut interactome in round/elongating spermatids

Project description:NUT, nuclear protein in testis is the universal fusion partner of BRD4 in the highly aggressive NUT Midline Carcinoma (NMC), but its physiological function was unknown. Here we show that Nut is exclusively expressed in post-meiotic spermatogenic cells, at the time of genome-wide histone hyperacetylation. Inactivation of Nut induces a spermatogenesis arrest at the histone-to-protamine replacement stage, leading to male infertility. Subsequent molecular investigations show that Nut sustains global histone H4 hyperacetylation in post-meiotic cells. Additionally, Nut mediates a p300/CBP-dependent gene expression program and, by enhancing acetylation of H4 at both K5 and K8 sites, provides binding sites for the first bromodomain of Brdt, which drives histone removal. Nut’s major function is therefore to use the ubiquitous HATs p300/CBP to direct a cell-type specific histone hyperacetylation. Its ectopic activity in NMC recreates a forced p300-induced histone hyperacetylation / bromodomain binding loop that normally operates in post-meiotic spermatogenic cells.

2018-10-02 | PXD008727 | Pride

ChIP-Seq of H4K5acK8ac and BRD2 in H23 NSCLC cell line treated with 500 nM JQ1 for 24h

Project description:Changes in acetylation of histone H4 are a common hallmark of cancer cells. In leukemia cells, histone H4 is characterized by loss of K16 mono-acetylation. Bromodomain proteins specifically recognize acetylated lysines and have been used as a target for anti cancer drug, JQ1 and iBET. Although acetylation and de-acetylation of histone H4 have been shown to have big impact in cancer cells, little attention has been focused on histone H4-acetylation at a genome level. To uncover potential epigenetic role of hyper-acetylated histone H4 at a genome-wide level in cancer cell, we generated a novel monoclonal antibody specifically recognizing histone H4 with at least two acetylated lysine residues (H4K5ac+K8ac). At the genome-wide level, hyper-acetylated histone H4 is associated with promoter and regulatory element (active enhancer, eRNA and super enhancer). We show that diacetylation at K5 and K8 of histone H4 co-localizes H3K27ac and BRD2 in the majority of active enhancer and promoters. However BRD2 has a stronger association with H4K5acK8ac. Furthermore we identified two specific chromatin states, which separately contain either H3K27ac or acetylated histone H4. Although JQ1 led to global reduction of BRD2 binding on the chromatin, only local changes of histone H4 multi-acetylation were observed upon BET inhibition by JQ1

2018-06-04 | GSE113714 | GEO

Nut is a cell type-specific stimulator of p300 enhancing H4 hyperacetylation during haploid male genome programming

Project description:NUT, nuclear protein in testis is the universal fusion partner of BRD4 in the highly aggressive NUT Midline Carcinoma (NMC), but its physiological function is unknown. Here we show that Nut is exclusively expressed in post-meiotic spermatogenic cells, at the time of genome-wide histone hyperacetylation. Inactivation of Nut induces a spermatogenesis arrest at the histone-to-protamine replacement stage, leading to male infertility. Subsequent molecular investigations show that Nut sustains global histone H4 hyperacetylation in post-meiotic cells. Additionally, Nut mediates a p300/CBP-dependent gene expression program and, by enhancing acetylation of H4 at both K5 and K8 sites, provides binding sites for the first bromodomain of Brdt, which drives histone removal. Our results bring the first evidence of Nut’s function in spermatogenic cells where it uses the ubiquitous HATs p300/CBP to direct a cell-type specific histone H4 hyperacetylation. The ectopic activity of Nut in NMC recreates a forced p300-induced histone hyperacetylation / bromodomain-binding loop that normally operates in post-meiotic spermatogenic cells.

2018-10-15 | GSE111931 | GEO

Nut directs p300-dependant genome-wide H4 hyperacetylation in male germ cells: transcriptomic data

Project description:NUT, nuclear protein in testis, is a universal oncogenic driver in the highly aggressive NUT Midline Carcinoma whose physiological function in male germ cells had so far remained unknown. Here we show that Nut’s expression is normally restricted to post-meiotic spermatogenic cells, where its presence triggers the p300-dependant genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone removal stage. Molecular investigations show that Nut uses CBP/p300 to enhance acetylation of H4 at both K5 and K8 providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which has long been known to occur prior to the final compaction of the male genome.

2018-10-15 | GSE118969 | GEO

ChIP-Seq of H4K5acK8ac, H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K9me3, H3K27me3 and BRD2 in H23 NSCLC cell line

Project description:The bromodomain and extra-terminal domain (BET) proteins are known as drug targets in diseases. However, the BET protein association profile to histone H4 hyperacetylation is not well understood and BET inhibition effects have been studied more in the context of BRD4 than BRD2. Here, by integrating chromatin and transcriptome analyses of ChIP-seq and Cap Analysis Gene Expression (CAGE) datasets, we show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Interestingly, although BET inhibition by JQ1 led to complete reduction of BRD2 binding, only local changes of H4K5acK8ac were observed and surprisingly a remarkable number of BRD2-bound genes including MYC and its target genes were upregulated. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors (TFs) potentially involved in the JQ1 response in BRD2-dependent and independent manner.

2018-06-04 | GSE104481 | GEO

CAGE profiling after treatment with JQ1 BET inhibitor in lung cancer cell line.

Project description:The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed, suggesting that recruitment of BRD2 does not influence global histone H4 hyperacetylation levels. This finding supports a model in which recruitment of BET proteins via histone H4 hyperacetylation is predominant over hyperacetylation of histone H4 by BET protein-associated acetyltransferases. In addition, we found a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and independent manner.

2018-06-04 | GSE113711 | GEO

ChIP-Seq of H4K5acK8ac in GM12878, K562

Project description:From: "JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states". The bromodomain and extra-terminal domain (BET) proteins are known as drug targets in diseases. However, the BET protein association profile to histone H4 hyperacetylation is not well understood and BET inhibition effects have been studied more in the context of BRD4 than BRD2. Here, by integrating chromatin and transcriptome analyses of ChIP-seq and Cap Analysis Gene Expression (CAGE) datasets, we show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Interestingly, although BET inhibition by JQ1 led to complete reduction of BRD2 binding, only local changes of H4K5acK8ac were observed and surprisingly a remarkable number of BRD2-bound genes including MYC and its target genes were upregulated. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors (TFs) potentially involved in the JQ1 response in BRD2-dependent and independent manner.

2018-06-04 | GSE113635 | GEO

Defining super-enhancers by highly ranked histone H4 multi-acetylation levels identifies transcription factors associated with glioblastoma stem-like properties

Project description:The bromodomain and extra-terminal domain (BET) family consists of acetyllysine-binding proteins involved in many cancers, including glioblastoma multiforme. While the BET family activates transcription through binding to hyperacetylated histone H4 with simultaneous acetylation of K5 and K8 (H4K5acK8ac), so far epigenomic analysis of the BET family has mainly focused on H3K27ac, which is not their binding target. Here, we have examined the epigenomic profiles, including H4K5acK8ac and a BET family protein, BRD4, along with transcriptomics using a BET inhibitor, JQ1, in three human glial cell lines. We found that the expression of genes in which H4K5acK8ac is preferred over H3K27ac at promoters was mostly downregulated upon JQ1 in a glioblastoma stem cell (GSC) line. Knockdown of genes with the H4K5acK8ac-preferred promoters diminished the stemness of GSC. By defining super-enhancers (SEs) ranked by H4K5acK8ac, we found that 43% of the H4K5acK8ac-ranked SE were different from H3K27ac-ranked SE in GSC. CRISPR-Cas9-mediated deletion of the H4K5acK8ac-preferred SEs reduced the expression of associated genes including MYCN and NFIC in GSC and diminished its stemness. These results validate a novel strategy to identify genes involved in the regulation of glioblastoma stemness, through histone H4 hyperacetylation.

2023-07-23 | GSE178471 | GEO

Mus musculus

Project description:Dynamic competing histone H4 K5K8 acetylation and butyrylation are hallmarks of highly active gene promoters

| PRJNA309951 | ENA

The HAT Inhibitor Anacardic Acid Leads to Changes in Global Gene Expression During in vitro P.falciparum Development

Project description:To better understand the role of histone lysine acetylation in transcription in Plasmodium falciparum, we sought to attenuate the histone acetyltransferase (HAT) activity of PfGCN5 using anacardic acid (AA). We showed that AA reversibly and noncompetitively inhibited the HAT activity of recombinant PfGCN5. To a lesser extent, AA inhibited the PfGCN5 activity in parasite nuclear extracts, but did not affect the histone deacetylase activity. AA blocked the growth of both chloroquine-sensitive and -resistant strains with a 50% inhibitory concentration of ~30 uM. Treatment of the parasites with 20 uM of AA for 12 h had no obvious effect on parasite growth or gross morphology, but induced hypoacetylation of histone H3 at K9 and K14, but not H4 at K5, K8, K12, and K16, suggesting of specific inhibition of the PfGCN5 HAT. Microarray analysis showed that this AA treatment disturbed the parasite transcription program, resulting in â¥2-fold change in the expression of 271 (~5%) parasite genes in late trophozoites, among which 207 genes were down-regulated. Interestingly, a significant proportion of the down-regulated genes is potentially associated with signal transduction and transcription. Furthermore, cluster analysis of gene expression indicated that AA mostly down-regulated active genes, and this gene pool significantly overlapped with that enriched for H3K9 acetylation. We further demonstrated by chromatin immunoprecipitation and real-time polymerase chain reaction that AA treatment reduced acetylation near the putative promoters of a set of down-regulated genes. The identification of AA as a PfGCN5 inhibitor offers a useful tool for further functional analysis of epigenetics in transcription regulation in malaria parasites. Late trophozoits were selected after AA treatment or untreated for RNA extraction and hybridization on microarrays. We sought to obtain the expression level changing after AA treatment.

2008-06-13 | E-GEOD-11763 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data