Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA172650 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The H2A variant H2AZ is essential for embryonic development and for proper execution of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions in H2AZ are likely key for its functional specialization, but we know little about how these differences contribute to chromatin regulation. Here, we show that the extended acidic patch, specifically the three divergent residues in the C-terminal docking domain, is necessary for lineage commitment during ESC differentiation and proper execution of gene expression programs during ESC differentiation. Surprisingly, disruption of the acidic patch domain has a distinct consequence on cellular specification compared to H2AZ depletion. This is consistent with differences in gene expression profiles of H2AZ M-bM-^@M-^Sdepleted and acidic patch (AP) mutant ESCs during early lineage commitment. Interestingly, the distinct consequence of AP mutant expression on gene regulation is coincidence with an altered destabilized chromatin state and high chromatin mobility dependent on active transcription. Collectively, our data shows that the divergent residues within the acidic patch domain are key structural determinants of H2AZ function and links chromatin structure and dynamics with gene regulation and cell fate specification. H2AZ extended acidic patch was mutated, or H2AZ was KD in mouse embryonic stem cells and RNA-Seq analysis was performed on the resulting cultures. Characterization of H2AZ-WT and -AP3-mutant binding specificities were performed by ChIP-Seq.
2013-09-23 | E-GEOD-40064 | biostudies-arrayexpress
Project description:The H2A variant H2AZ is essential for embryonic development and for proper execution of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions in H2AZ are likely key for its functional specialization, but we know little about how these differences contribute to chromatin regulation. Here, we show that the extended acidic patch, specifically the three divergent residues in the C-terminal docking domain, is necessary for lineage commitment during ESC differentiation and proper execution of gene expression programs during ESC differentiation. Surprisingly, disruption of the acidic patch domain has a distinct consequence on cellular specification compared to H2AZ depletion. This is consistent with differences in gene expression profiles of H2AZ M-bM-^@M-^Sdepleted and acidic patch (AP) mutant ESCs during early lineage commitment. Interestingly, the distinct consequence of AP mutant expression on gene regulation is coincidence with an altered destabilized chromatin state and high chromatin mobility dependent on active transcription. Collectively, our data shows that the divergent residues within the acidic patch domain are key structural determinants of H2AZ function and links chromatin structure and dynamics with gene regulation and cell fate specification. H2AZ extended acidic patch was mutated, or H2AZ was KD in mouse embryonic stem cells and RNA-Seq analysis was performed on the resulting cultures. Characterization of H2AZ-WT and -AP3-mutant binding specificities were performed by ChIP-Seq.
2013-09-23 | E-GEOD-40063 | biostudies-arrayexpress
Project description:H2AZ extended acidic patch is necessary for formation specialized chromatin states in ESCs [RNA-Seq]
| PRJNA172651 | ENA
Project description:The H2A variant H2AZ is essential for embryonic development and for proper execution of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions in H2AZ are likely key for its functional specialization, but we know little about how these differences contribute to chromatin regulation. Here, we show that the extended acidic patch, specifically the three divergent residues in the C-terminal docking domain, is necessary for lineage commitment during ESC differentiation and proper execution of gene expression programs during ESC differentiation. Surprisingly, disruption of the acidic patch domain has a distinct consequence on cellular specification compared to H2AZ depletion. This is consistent with differences in gene expression profiles of H2AZ –depleted and acidic patch (AP) mutant ESCs during early lineage commitment. Interestingly, the distinct consequence of AP mutant expression on gene regulation is coincidence with an altered destabilized chromatin state and high chromatin mobility dependent on active transcription. Collectively, our data shows that the divergent residues within the acidic patch domain are key structural determinants of H2AZ function and links chromatin structure and dynamics with gene regulation and cell fate specification.
2013-09-23 | GSE40063 | GEO
Project description:The H2A variant H2AZ is essential for embryonic development and for proper execution of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions in H2AZ are likely key for its functional specialization, but we know little about how these differences contribute to chromatin regulation. Here, we show that the extended acidic patch, specifically the three divergent residues in the C-terminal docking domain, is necessary for lineage commitment during ESC differentiation and proper execution of gene expression programs during ESC differentiation. Surprisingly, disruption of the acidic patch domain has a distinct consequence on cellular specification compared to H2AZ depletion. This is consistent with differences in gene expression profiles of H2AZ –depleted and acidic patch (AP) mutant ESCs during early lineage commitment. Interestingly, the distinct consequence of AP mutant expression on gene regulation is coincidence with an altered destabilized chromatin state and high chromatin mobility dependent on active transcription. Collectively, our data shows that the divergent residues within the acidic patch domain are key structural determinants of H2AZ function and links chromatin structure and dynamics with gene regulation and cell fate specification.
2013-09-23 | GSE40064 | GEO
Project description:We employed MNase-seq and ChIP-seq to determine irregularities in chromatin architecture in mutants of the nucleosome acidic patch. Indeed, the acidic patch mutant showed defects in nucleosome positioning and occupancy at genes with high expression and H2B K123ub levels, linking the acidic patch to transcription-dependent chromatin changes. Our results emphasize the importance of the nucleosome core as a hub for proteins that regulate chromatin during transcription.
2019-06-11 | GSE121543 | GEO
Project description:Elucidating how chromatin organization influences gene expression patterns and ultimately cell fate is fundamental to understanding development and disease. Histone variants have emerged as key regulators of genome function by creating specialized chromatin domains. The histone variant H2AZ plays an essential, but poorly understood function during early mammalian development. Genome-wide analysis reveals that H2AZ is enriched at a large class of developmentally important genes that are known targets of Polycomb-mediated repression in embryonic stem (ES) cells. H2AZ displays a highly defined spatial patterning that is remarkably similar to the Polycomb group (PcG) protein Suz12 in ES cells, but not in differentiated cell types. By using RNA interference, we demonstrate that H2AZ is a critical regulatory component at developmental genes in ES cells and show that localization of H2AZ and PcG proteins is interdependent at target promoters. Moreover, similarly to Suz12, H2AZ is required for lineage commitment. This study reveals a connection between H2AZ and PcG proteins in ES cells and suggests that these factors functionally interact to regulate chromatin states necessary for the proper execution of developmental gene expression programs.
2009-01-22 | E-TABM-556 | biostudies-arrayexpress
Project description:The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. In order to define the molecular basis of acidic patch recognition proteome-wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K36) demethylase KDM2A, but not its closely related paralog, KDM2B, requires the acidic patch for nucleosome binding. These KDM2 family JumonjiC (JmjC) domain lysine demethylases are critical to heterochromatin formation and are commonly misregulated in cancer. Despite fundamental roles in transcriptional regulation in health and disease, the molecular mechanisms governing nucleosome substrate specificity of KDM2A/B, or any other JmjC lysine demethylases, remain unclear. We used a covalent JmjC inhibitor to solve cryo-EM structures of KDM2A and KDM2B trapped in action on the nucleosome. Our structures show that KDM2-nucleosome binding is paralog-specific and facilitated by dynamic nucleosomal DNA unwrapping and histone charge shielding that mobilize the H3K36 sequence for demethylation.
2023-02-14 | PXD032791 | Pride
Project description:Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While structural and biochemical studies of individual nucleosome interactions have suggested that an acidic patch on the nucleosome disk surface may be a common site for recruitment to chromatin, the pervasiveness of acidic patch binding and whether other nucleosome surface binding hot-spots exist remains unclear. Here, we use nucleosome affinity proteomics with a library of nucleosomes that collectively disrupts all exposed histone surfaces to establish the universal principles of nucleosome binding. We find that the acidic patch and two adjacent surfaces are the primary hot-spots for nucleosome disk binding and are critical for the majority of nucleosome-protein interactions. In contrast, nearly half of the nucleosome disk surface participates only minimally in protein binding. In addition to establishing the fundamental principles of chromatin binding, our screen defines nucleosome surface requirements of nearly 300 nucleosome interacting proteins implicated in diverse nuclear processes including transcription, DNA damage repair, cell cycle regulation, and nuclear architecture. Building from our screen, we demonstrate that the Anaphase-Promoting Complex/Cyclosome directly binds the acidic patch and elucidate a redundant charge-based mechanism of acidic patch binding by nuclear pore protein ELYS. Overall, our interactome screen illuminates a highly competitive nucleosome binding hub for chromatin-targeted activities and curates a list of nucleosome interacting proteins that will enable mechanistic exploration of many unexpected chromatin-templated nuclear processes.
2020-06-24 | PXD018690 | Pride