Novel contribution of acetylated histone variant H2A.Z in activation of neo-enhancers in prostate cancer
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PROVIDER: PRJNA306938 | ENA |
REPOSITORIES: ENA
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Project description:Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodelled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Together these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.
2017-09-05 | GSE76336 | GEO
Project description:Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodelled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Together these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.
2017-09-05 | GSE76335 | GEO
Project description:Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodelled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Together these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.
2017-09-05 | GSE76334 | GEO
Project description:Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.
| S-EPMC5676741 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-09-05 | GSE76337 | GEO
Project description:The incorporation of histone variant H2A.Z, a conserved H2A variant, into nucleosomes creates specialized chromatin domains that regulate DNA-templated processes, including transcription. H2A.Z-containing nucleosomes may poise gene regulatory regions for transcription, but mechanistic details are lacking. In Saccharomyces cerevisiae, the diverging H2A.Z C-terminus is thought to provide the H2A.Z exclusive functions. To elucidate the roles of this H2A.Z C-terminus genome wide, we made use of derivatives where the C-terminus was replaced with the corresponding region of H2A (ZA protein), or the H2A region plus a transcriptional activating peptide, with the idea of regenerating the H2A.Z-dependent regulation globally. An assessment of the genome-wide distribution of these H2A.Z derivatives shows that the H2A.Z C-terminal region is crucial for both maintaining the occupation level of H2A.Z and the proper positioning of the targeted nucleosomes. Interestingly, the specific contribution on incorporation efficiency vs nucleosome positioning varies enormously, depending on loci analyzed. For the ZA protein, positioning changes most importantly near origins of replication and snoRNA gene promoters, while incorporation is affected on all other sites. Furthermore, the role of H2A.Z in global transcription regulation also depends on its C-terminal region. Remarkably however, the latter mostly involves genes without a H2A.Z nucleosome in the promoter.
2022-08-18 | GSE156492 | GEO
Project description:The involvement of the histone variant H2A.Z and its isoforms in the regulation of gene expression is an increasing exciting field considering the impact of such regulations in physio-pathology. Indeed, we and other recently showed that H2A.Z.1 and H2A.Z.2 isoforms exert cooperative or antagonistic transcriptional regulations on subsets of genes involved in key processes, such as proliferation, senescence or several organ functions. In this work, we analyze the relative role of both H2A.Z isoforms on parameters of the intestinal epithelial homeostasis. We observed that the amount of H2A.Z.1 and H2A.Z.2 at TSS and gene bodies are highly correlated and that the two H2A.Z isoforms can replace each other when depleted. We highlighted the role of their respective deposition onto chromatin by specific incorporators in some discrete isoform-specific contribution to the differentiation process. We have also uncovered an unexpected link between H2A.Z isoforms occupancy at gene bodies and the propensity of genes to be induced in enterocyte differentiation.
2024-10-15 | GSE232113 | GEO
Project description:The involvement of the histone variant H2A.Z and its isoforms in the regulation of gene expression is an increasing exciting field considering the impact of such regulations in physio-pathology. Indeed, we and other recently showed that H2A.Z.1 and H2A.Z.2 isoforms exert cooperative or antagonistic transcriptional regulations on subsets of genes involved in key processes, such as proliferation, senescence or several organ functions. In this work, we analyze the relative role of both H2A.Z isoforms on parameters of the intestinal epithelial homeostasis. We observed that the amount of H2A.Z.1 and H2A.Z.2 at TSS and gene bodies are highly correlated and that the two H2A.Z isoforms can replace each other when depleted. We highlighted the role of their respective deposition onto chromatin by specific incorporators in some discrete isoform-specific contribution to the differentiation process. We have also uncovered an unexpected link between H2A.Z isoforms occupancy at gene bodies and the propensity of genes to be induced in enterocyte differentiation.
2024-10-15 | GSE232112 | GEO
Project description:The regulation of eukaryotic chromatin relies on interactions between many epigenetic factors, including histone modifications, DNA methylation, and the incorporation of histone variants. H2A.Z, one of the most conserved but enigmatic histone variants that is enriched at the transcriptional start sites of genes, has been implicated in a variety of chromosomal processes. Recently, we reported a genome-wide anticorrelation between H2A.Z and DNA methylation, an epigenetic hallmark of heterochromatin that has also been found in the bodies of active genes in plants and animals. Here, we investigate the basis of this anticorrelation using a novel h2a.z loss-of-function line in Arabidopsis thaliana. Through genome-wide bisulfite sequencing, we demonstrate that a loss of H2A.Z in Arabidopsis does not affect the level or profile of DNA methylation in genes, and we propose that the global anticorrelation between DNA methylation and H2A.Z is caused by the exclusion of H2A.Z from methylated DNA. RNA-seq and genomic mapping of H2A.Z show that H2A.Z enrichment across gene bodies, rather than at the TSS, is correlated with lower transcription levels and higher measures of gene responsiveness. We find that a loss of H2A.Z causes misregulation of many genes that are disproportionately associated with response to both endogenous and exogenous stimuli. We propose that H2A.Z deposition in gene bodies promotes variability in levels and patterns of gene expression, and that a major function of genic DNA methylation is to exclude H2A.Z from constitutively expressed genes. Examination of DNA methylation and transcription in an h2a.z mutant
2012-12-13 | E-GEOD-39045 | biostudies-arrayexpress
Project description:Gene regulatory programs in different cell types are largely defined through cell-specific enhancers activity. The histone variant H2A.Z has been shown to play important roles in transcription mainly by controlling proximal promoters, but its effect on enhancer functions remains unclear. Here, we demonstrate by genome-wide approaches that H2A.Z is present at a subset of active enhancers bound by the estrogen receptor alpha (ERα). We also determine that H2A.Z does not influence the local nucleosome positioning around ERα-enhancers using ChIP-sequencing at nucleosomal resolution and unsupervised pattern discovery. We further highlight that H2A.Z-enriched enhancers are associated with chromatin accessibility, H3K122ac enrichment and hypomethylated DNA. Moreover, upon estrogen stimulation, the enhancers occupied by H2A.Z produce enhancer RNAs (eRNAs), and recruit RNA polymerase II as well as RAD21, a member of the cohesin complex involved in chromatin interactions between enhancers and promoters. Importantly, their recruitment and eRNAs production are abolished by H2A.Z depletion, thereby revealing a novel functional link between H2A.Z occupancy and enhancer activity. Taken together, our findings suggest that H2A.Z acts as an important player for enhancer functions by establishing and maintaining a chromatin environment required for RNA polymerase II recruitment, eRNAs transcription and enhancer-promoters interactions, all essential attributes of enhancer activity. The MNase ChIP-seqs in this study measure the genome-wide binding landscape of H2A.Z, H3K4me1, H3K27ac and H3K4me3 in MCF-7 cells in the absence or presence of E2. Two biological replicates were done for each ChIP-seq experiment and for each condition, as well as, control input.
2015-08-31 | E-GEOD-57436 | biostudies-arrayexpress