Potential Roles of H2A.Z Ubiquitination
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA738691 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14851102.fastq.gz | Fastqsanger.gz | |||
| SRR14851103.fastq.gz | Fastqsanger.gz |
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Project description:Nucleosome is a highly dynamic macromolecular complex that is assembled and remodeled by the replacement of major histone variant H2A.Z, thereby affecting nucleosome structure and stability.Here we established two cell lines stably overexpressing wild-type H2A.Z and mutant H2A.Z with ubiquitination deficiency to explore the potential effects caused by H2A.Z ubiquitination. Intriguingly, H2A.Z ubiquitination was first revealed to enhance the stability of H2A-H2A.Z heterotypic nucleosomes. Chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-Seq) further revealed that H2A.Z ubiquitination played a crucial role in the transcriptional regulation.
2021-06-30 | GSE178363 | GEO
Project description:The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin. Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles. Examination of histone variant, histone modifications and transcription machinery in 3 cell types
2012-07-19 | E-GEOD-39237 | biostudies-arrayexpress
Project description:The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin. Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles.
2012-07-20 | GSE39237 | GEO
Project description:Affinity Purification Mass Spectrometry (AP-MS) of Drosophila ovaries expressing an H2A.Z-FlagHA transgene to identify interacting partners of H2A.Z to elucidate potential maternally supplied histone chaperones that deposit H2A.Z on the transcription start site (TSS).
2022-02-15 | PXD029061 | Pride
Project description:The histone variant H2A.Z plays important functions in the regulation of gene expression. In mammals, it is encoded by two genes, giving rise to two highly related isoforms named H2A.Z.1 and H2A.Z.2, which can have similar or antagonistic functions depending on the promoter. Knowledge of the physiopathological consequences of such functions emerges, but how the balance between these isoforms regulates tissue homeostasis is not fully understood. Here, we investigated the relative role of H2A.Z isoforms in intestinal epithelial homeostasis. Through genome-wide analysis of H2A.Z genomic localization in differentiating Caco-2 cells, we uncovered an enrichment of H2A.Z isoforms on the bodies of genes which are induced during enterocyte differentiation, stressing the potential importance of H2A.Z isoforms dynamics in this process. Through a combination of in vitro and in vivo experiments, we further demonstrated the two isoforms cooperate for stem and progenitor cells proliferation, as well as for secretory lineage differentiation. However, we found that they antagonistically regulate enterocyte differentiation, with H2A.Z.1 preventing terminal differentiation and H2A.Z.2 favoring it. Altogether, these data indicate that H2A.Z isoforms are critical regulators of intestine homeostasis and may provide a paradigm of how the balance between two isoforms of the same chromatin structural protein can control physiopathological processes.
2024-10-14 | GSE232114 | GEO
Project description:Potential Roles of IGF2BP3 in Bladder Cancer
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Project description:The histone variant H2A.Z plays key roles in gene expression, DNA repair, and centromere function. H2A.Z deposition is controlled by SWR-C chromatin remodeling enzymes that catalyze the nucleosomal exchange of canonical H2A with H2A.Z. Here we report that acetylation of histone H3 lysine 56 (H3-K56Ac) alters the substrate specificity of SWR-C, leading to promiscuous dimer exchange where either H2A.Z or H2A can be exchanged from nucleosomes. This result is confirmed in vivo, where genome-wide analysis demonstrates widespread decreases in H2A.Z levels in yeast mutants with hyperacetylated H3K56. Our work also suggests that a conserved SWR-C subunit may function as a M-bM-^@M-^\lockM-bM-^@M-^] that prevents removal of H2A.Z from nucleosomes. Our study identifies a histone modification that regulates a chromatin remodeling reaction and provides insights into how histone variants and nucleosome turnover can be controlled by chromatin regulators. H2A.Z ChIP seq experiments in mutants with constitutive H3K56ac
2013-04-15 | E-GEOD-43935 | biostudies-arrayexpress
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: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
Project description:H2A.Z is a H2A-type histone variant essential for many aspects of cell biology, ranging from gene expression to genome stability. From deuterostomes, H2A.Z evolved into two paralogues, H2A.Z.1 and H2A.Z.2, that differ by only three amino acids and are encoded by different genes (H2AFZ and H2AFV, respectively). Despite the importance of this histone variant in development and cellular homeostasis, very little is known about the individual functions of each paralogue in mammals. Here, we have investigated the distinct roles of the two paralogues in cell cycle regulation and unveiled non-redundant functions for H2A.Z.1 and H2A.Z.2 in cell division. Our findings show that H2A.Z.1 regulates the expression of cell cycle genes such as Myc and Ki-67 and its depletion leads to a G1 arrest and cellular senescence. On the contrary, H2A.Z.2, in a transcription independent manner, is essential for centromere integrity and sister chromatid cohesion regulation, thus playing a key role in chromosome segregation.
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