Genome-wide chromatin state in myoblasts lacking Hira [ChIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE161054 | GEO | 2021/05/03
REPOSITORIES: GEO
Similar Datasets
Project description:The epigenetic mechanisms coordinating the maintenance of adult cellular lineages and the inhibition of alternative cell fates are poorly understood. Here we show that targeted ablation of the histone chaperone HIRA in myogenic cells leads to extensive transcriptional modifications consistent with a major role in maintaining skeletal muscle cellular identity. Conditional ablation of HIRA in muscle stem cells of adult mice compromised their capacity to regenerate and self-renew, leading to tissue repair failure. Epigenetic analysis of Hira-deficient cells showed a drastic reduction of histone variant H3.3 deposition and H3K27ac modification at regulatory regions of muscle genes. By contrast, genes from alternative lineages were ectopically expressed in Hira-mutant cells via MLL1/MLL2-mediated increase of H3K4me3 mark at silent promoter regions. Therefore, HIRA sustains the epigenetic landscape governing muscle cell lineage identity via incorporation of H3.3 at muscle gene regulatory regions, while preventing the expression of alternative lineage genes.
2021-05-03 | GSE161055 | GEO
Project description:The epigenetic mechanisms coordinating the maintenance of adult cellular lineages and the inhibition of alternative cell fates are poorly understood. Here we show that targeted ablation of the histone chaperone HIRA in myogenic cells leads to extensive transcriptional modifications consistent with a major role in maintaining skeletal muscle cellular identity. Conditional ablation of HIRA in muscle stem cells of adult mice compromised their capacity to regenerate and self-renew, leading to tissue repair failure. Epigenetic analysis of Hira-deficient cells showed a drastic reduction of histone variant H3.3 deposition and H3K27ac modification at regulatory regions of muscle genes. By contrast, genes from alternative lineages were ectopically expressed in Hira-mutant cells via MLL1/MLL2-mediated increase of H3K4me3 mark at silent promoter regions. Therefore, HIRA sustains the epigenetic landscape governing muscle cell lineage identity via incorporation of H3.3 at muscle gene regulatory regions, while preventing the expression of alternative lineage genes.
2021-05-03 | GSE161053 | GEO
Project description:The epigenetic mechanisms coordinating the maintenance of adult cellular lineages and the inhibition of alternative cell fates are poorly understood. Here we show that targeted ablation of the histone chaperone HIRA in myogenic cells leads to extensive transcriptional modifications consistent with a major role in maintaining skeletal muscle cellular identity. Conditional ablation of HIRA in muscle stem cells of adult mice compromised their capacity to regenerate and self-renew, leading to tissue repair failure. Epigenetic analysis of Hira-deficient cells showed a drastic reduction of histone variant H3.3 deposition and H3K27ac modification at regulatory regions of muscle genes. By contrast, genes from alternative lineages were ectopically expressed in Hira-mutant cells via MLL1/MLL2-mediated increase of H3K4me3 mark at silent promoter regions. Therefore, HIRA sustains the epigenetic landscape governing muscle cell lineage identity via incorporation of H3.3 at muscle gene regulatory regions, while preventing the expression of alternative lineage genes.
2021-05-03 | GSE167911 | GEO
Project description:Cellular metabolism and chromatin landscape both contribute to cell fate determination. However, their interplay remains poorly understood. Here we show that Prohibitin (PHB), an evolutionarily conserved protein, involves in a histone variant H3.3 chaperon HIRA complex-dependent epigenetic and metabolic circuitry to maintain the identity of human embryonic stem cells (hESCs). We found that silencing of PHB triggers hESC differentiation with concomitant enhancements of histone 3 (H3) lysine (K) methyl modifications as a result of the reduced production of α-ketoglutarate (α-KG), a metabolite required for activities of many dioxygenase and in turn chromatin structure1,2. Mechanistically, PHB acts as a functional member of the HIRA complex3,4. Resembling PHB deficiency, loss of HIRA in hESCs leads to massive differentiation and aberrant histone modifications, although it was previously found not to disrupt the self-renewal in mouse ESCs (mESCs)5. Genome-wide H3.3 ChIP- sequence analyses indicate that reduction of H3.3 deposition caused by PHB knock down is extremely similar to that induced by HIRA knock down. Specifically, silencing either HIRA or PHB leads to repressive chromatin characters at promoters of pluripotency genes and isocitrate dehydrogenases (IDHs), the enzyme responsible for α-KG production, but active chromatin features at promoters of developmental genes, paralleling to transcript levels of these genes. Our results identify PHB as an essential factor not only for hESC self-renewal but also for the proper function of the HIRA complex, linking the HIRA complex-dependent H3.3 deposition to the production of a critical metabolite required for shaping chromatin structure, and demonstrating the importance of the interplay between epigenetic state and metabolic regulation in cell fate determination. Examination of H3.3 deposition in NT, PHB, and HIRA siRNA treated hESCs respectively.
2016-08-11 | E-GEOD-72143 | biostudies-arrayexpress
Project description:Establishment of a proper chromatin landscape is central to genome function. Here, we explain H3 variant distribution by specific targeting and dynamics of deposition involving the CAF-1 and HIRA histone chaperones. Impairing replicative H3.1 incorporation via CAF-1 enables an alternative H3.3 deposition at replication sites via HIRA. Conversely, the H3.3 incorporation throughout the cell cycle via HIRA cannot be replaced by H3.1. ChIP-seq analyses reveal correlation between HIRA-dependent H3.3 accumulation and RNA pol II at transcription sites and specific regulatory elements, further supported by their biochemical association. Remarkably, the HIRA complex shows unique DNA binding properties and depleting HIRA increases DNA sensitivity to nucleases. We propose that protective gap-filling of naked DNA by HIRA leads to a broad distribution of H3.3, and HIRA association with Pol II ensures local H3.3 enrichment at specific sites. Examination of genome-wide localization of two histone H3 variants.
2011-12-16 | E-GEOD-31794 | biostudies-arrayexpress
Project description:Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Histone chaperone HIRA deposits nucleosome-destabilizing histone variant H3.3 into chromatin in a DNA replication-independent manner. Histone H3.3 and a subset of other typically M-bM-^@M-^\replication-dependentM-bM-^@M-^] core histones were expressed in non-proliferating senescent cells, the latter linked to alternative mRNA splicing and polyadenylation. Senescent cells incorporated newly-synthesized histones into chromatin, partially dependent on HIRA. HIRA and newly-deposited histone H3.3 co-localized at promoters of expressed genes, and their distribution shifted between proliferating and senescent cells, paralleling changes in gene expression. In senescent cells, gene promoters showed exceptional enrichment of a histone acetylation linked to open and dynamic chromatin, H4K16ac. Abundance of H4K16ac depended on HIRA. In the mouse, inactivation of HIRA downregulated H4K16ac and dramatically enhanced oncogene-induced hyperplasia. To conclude, HIRA controls a previously undefined dynamic non-canonical H4K16ac-decorated chromatin landscape in senescence, and also plays an unanticipated role in suppression of oncogene-induced neoplasia. Examination of HIRA protein binding alongside histone modification H4K16ac and H3.3 in proliferating and senescent IMR90 cells
2014-11-26 | E-GEOD-56307 | biostudies-arrayexpress
Project description:Establishment of a proper chromatin landscape is central to genome function. Here, we explain H3 variant distribution by specific targeting and dynamics of deposition involving the CAF-1 and HIRA histone chaperones. Impairing replicative H3.1 incorporation via CAF-1 enables an alternative H3.3 deposition at replication sites via HIRA. Conversely, the H3.3 incorporation throughout the cell cycle via HIRA cannot be replaced by H3.1. ChIP-seq analyses reveal correlation between HIRA-dependent H3.3 accumulation and RNA pol II at transcription sites and specific regulatory elements, further supported by their biochemical association. Remarkably, the HIRA complex shows unique DNA binding properties and depleting HIRA increases DNA sensitivity to nucleases. We propose that protective gap-filling of naked DNA by HIRA leads to a broad distribution of H3.3, and HIRA association with Pol II ensures local H3.3 enrichment at specific sites.
2011-12-16 | GSE31794 | GEO
Project description:Histone chaperones and chromatin remodelers control nucleosome dynamics, essential for transcription, replication, and DNA repair. The histone chaperone Anti-Silencing Factor 1 (ASF1) plays a central role in facilitating CAF-1-mediated replication-dependent H3.1 deposition and HIRA-mediated replication-independent H3.3 deposition in yeast and metazoans. Whether ASF1 function is evolutionarily conserved in plants is unknown. Here, we show that Arabidopsis ASF1 proteins display an exclusive preference for the H3.3-depositing HIRA complex. Simultaneous mutation of both Arabidopsis ASF1 genes caused a decrease in chromatin density and ectopic H3.1 occupancy at loci typically enriched with H3.3. Genetic, transcriptomic, and proteomic data indicate that ASF1 proteins strongly prefer the HIRA complex over CAF-1. asf1 mutants also displayed an increase in spurious Pol II transcriptional initiation, and showed defects in the maintenance of gene body CG DNA methylation and in the distribution of histone modifications. Furthermore, ectopic targeting of ASF1 caused excessive histone deposition, less accessible chromatin, and gene silencing. These findings reveal the importance of ASF1-mediated H3.3-H4 deposition via the HIRA pathway for proper epigenetic regulation of the genome.
2022-10-31 | PXD035578 | Pride
Project description:The incorporation of histone variant H3.3 has been implicated in the formation and maintenance of specialized chromatin structure in metazoan cells. H3.3 is enriched in promoters, regulatory elements and genebody, and HIRA is required for H3.3 enrichment in these regions. But the mechanism of regulating H3.3 deposition by HIRA remains elusive. By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators, we identify single-stranded DNA binding protein RPA as being critically required for deposition of newly synthesized H3.3. RPA interacts with HIRA and H3.3 and co-localizes with HIRA at gene promoters and some regulatory elements across genome wide. Deletion of RPA dramatically reduces the enrichment of HIRA and newly synthesized H3.3 at these regions and reduced nascent anti-sense transcription. Taken together, our data demonstrate that RPA functions as new regulator of H3.3 deposition in promoter and some regulatory elements by recruiting HIRA and reveal a novel mechanism for RPA in chromatin and gene regulation.
2016-12-07 | GSE76661 | GEO
Project description:Cellular metabolism and chromatin landscape both contribute to cell fate determination. However, their interplay remains poorly understood. Here we show that Prohibitin (PHB), an evolutionarily conserved protein, involves in a histone variant H3.3 chaperon HIRA complex-dependent epigenetic and metabolic circuitry to maintain the identity of human embryonic stem cells (hESCs). We found that silencing of PHB triggers hESC differentiation with concomitant enhancements of histone 3 (H3) lysine (K) methyl modifications as a result of the reduced production of α-ketoglutarate (α-KG), a metabolite required for activities of many dioxygenase and in turn chromatin structure1,2. Mechanistically, PHB acts as a functional member of the HIRA complex3,4. Resembling PHB deficiency, loss of HIRA in hESCs leads to massive differentiation and aberrant histone modifications, although it was previously found not to disrupt the self-renewal in mouse ESCs (mESCs)5. Genome-wide H3.3 ChIP- sequence analyses indicate that reduction of H3.3 deposition caused by PHB knock down is extremely similar to that induced by HIRA knock down. Specifically, silencing either HIRA or PHB leads to repressive chromatin characters at promoters of pluripotency genes and isocitrate dehydrogenases (IDHs), the enzyme responsible for α-KG production, but active chromatin features at promoters of developmental genes, paralleling to transcript levels of these genes. Our results identify PHB as an essential factor not only for hESC self-renewal but also for the proper function of the HIRA complex, linking the HIRA complex-dependent H3.3 deposition to the production of a critical metabolite required for shaping chromatin structure, and demonstrating the importance of the interplay between epigenetic state and metabolic regulation in cell fate determination.
2016-08-11 | GSE72143 | GEO