The role of histone variant H3.3 regulation by HIRA in hematopoiesis (ATAC-Seq)
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PROVIDER: PRJNA684566 | ENA |
REPOSITORIES: ENA
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Project description:Histone variants contribute to the complexity of the chromatin landscape and play an integral role in defining DNA domains and regulating gene expression. The histone H3 variant H3.3 is incorporated into genic elements independent of DNA replication by its chaperone HIRA. Here we demonstrate that Hira is required for the self-renewal of adult hematopoietic stem cells (HSCs) and to restrain erythroid differentiation. Deletion of Hira led to rapid depletion of HSCs while differentiated hematopoietic cells remained largely unaffected. Depletion of HSCs after Hira deletion was accompanied by increased expression of bivalent and erythroid genes, which were exacerbated upon cell division and paralleled increased erythroid differentiation. Assessing H3.3 occupancy identified a subset of polycomb-repressed chromatin in HSCs that depend on HIRA to maintain the inaccessible, H3.3-occupied state for gene repression. HIRA-dependent H3.3 incorporation thus defines distinct repressive chromatin that represses erythroid differentiation of HSCs.
2021-07-08 | GSE163198 | GEO
Project description:Histone variants contribute to the complexity of the chromatin landscape and play an integral role in defining DNA domains and regulating gene expression. The histone H3 variant H3.3 is incorporated into genic elements independent of DNA replication by its chaperone HIRA. Here we demonstrate that Hira is required for the self-renewal of adult hematopoietic stem cells (HSCs) and to restrain erythroid differentiation. Deletion of Hira led to rapid depletion of HSCs while differentiated hematopoietic cells remained largely unaffected. Depletion of HSCs after Hira deletion was accompanied by increased expression of bivalent and erythroid genes, which were exacerbated upon cell division and paralleled increased erythroid differentiation. Assessing H3.3 occupancy identified a subset of polycomb-repressed chromatin in HSCs that depend on HIRA to maintain the inaccessible, H3.3-occupied state for gene repression. HIRA-dependent H3.3 incorporation thus defines distinct repressive chromatin that represses erythroid differentiation of HSCs.
2021-07-08 | GSE163051 | GEO
Project description:Histone variants contribute to the complexity of the chromatin landscape and play an integral role in defining DNA domains and regulating gene expression. The histone H3 variant H3.3 is incorporated into genic elements independent of DNA replication by its chaperone HIRA. Here we demonstrate that Hira is required for the self-renewal of adult hematopoietic stem cells (HSCs) and to restrain erythroid differentiation. Deletion of Hira led to rapid depletion of HSCs while differentiated hematopoietic cells remained largely unaffected. Depletion of HSCs after Hira deletion was accompanied by increased expression of bivalent and erythroid genes, which were exacerbated upon cell division and paralleled increased erythroid differentiation. Assessing H3.3 occupancy identified a subset of polycomb-repressed chromatin in HSCs that depend on HIRA to maintain the inaccessible, H3.3-occupied state for gene repression. HIRA-dependent H3.3 incorporation thus defines distinct repressive chromatin that represses erythroid differentiation of HSCs.
2021-07-08 | GSE163050 | GEO
Project description:The role of histone variant H3.3 regulation by HIRA in hematopoiesis
| PRJNA684562 | ENA
Project description:HIRA is a histone chaperone that deposits the histone variant H3.3 in transcriptionally active genes. HIRA is essential for mouse development, as the standard knockout (KO) results in early embryonic death. However, the role of HIRA in hematopoiesis is poorly understood. We investigated the effect of Hira KO on hematopoiesis using Vav-Cre Loxp system. We show that Hira KO dramatically reduces bone marrow LSK cells, resulting in anemia, thrombopenia and severe, combined immunodeficiency. To investigate the molecular mechanisms, RNA-seq and ATAC-Seq were performed using LSK cells isolated from WT and Hira conditional KO mice.
2020-06-30 | GSE125154 | GEO
Project description:The role of histone variant H3.3 regulation by HIRA in hematopoiesis (RNA-seq)
| PRJNA685179 | ENA
Project description:The role of histone variant H3.3 regulation by HIRA in hematopoiesis (ChIP-Seq)
| PRJNA684567 | ENA
Project description:The incorporation of histone H3 variants has been implicated in the epigenetic memory of cellular state. Using genome editing with zinc finger nucleases to tag endogenous H3.3, we report genome-wide profiles of H3 variants in mammalian embryonic stem (ES) cells and neuronal precursor cells. Genome-wide patterns of H3.3 are dependent on amino acid sequence, and change with cellular differentiation at developmentally regulated loci. The H3.3 chaperone Hira is required for H3.3 enrichment at active and repressed genes. Strikingly, Hira is not essential for localization of H3.3 at telomeres and many transcription factor binding sites. Immunoaffinity purification and mass spectrometry reveal that the proteins Atrx and Daxx associate with H3.3 in a Hira-independent manner. Atrx is required for Hira-independent localization of H3.3 at telomeres, and for the repression of telomeric RNA. Our data demonstrate that multiple and distinct factors are responsible for H3.3 localization at specific genomic locations in mammalian cells. Crosslinking ChIP-seq: Examination of 1 histone variant (H3.3), 2 histone modifications, and Serine-5 phosphorylated RNA polymerase in 2 different cell types (H3.3-HA ES samples 1-4, and H3.3-HA NPC samples 7-10). Examination of 1 histone variant (H3.2), and one histone modification (H3K36me3) in 2 different cell types (H3.2-HA ES samples 5-6, and H3.2-HA NPC samples 11-12). Examination of 1 histone variant (H3.3), input control, and one histone modification (H3K36me3) in one cell type (H3.3-HA hybrid ES, samples 13-15). Examination of 1 histone variant (H3.1S31), input control, and one histone modification (H3K36me3) in one cell type (H3.1S31-HA hybrid ES, samples 16-18). Native ChIP-seq: Examination of 1 histone variant (H3.3), input control, and one histone modification (H3K4me3) in one cell type (H3.3-HA ES, samples 19-21). Examination of 1 histone variant (H3.2), input control, and two histone modifications (H3K4me3 and H3K27me3) in one cell type (H3.2-HA ES, samples 22-25). Examination of 1 histone variant (H3.3), input control, and two histone modifications (H3K4me1 and H3K36me3) in one cell type (H3.3-EYFP ES, samples 26-29). Examination of 1 histone variant (H3.3), input control, and two histone modifications (H3K4me1 and H3K36me3) in one cell type (Hira -/- H3.3-EYFP ES, samples 30-33). Examination of 1 histone variant (H3.3) and input control in one cell type (Atrxflox H3.3-EYFP ES, samples 34-37). Examination of HA antibody background in one cell type (wild-type ES, sample 38).
2010-03-04 | E-GEOD-16893 | biostudies-arrayexpress
Project description:To study the function of histone variant H3.3 pathway in androgen receptor-driven transcription in prostate cancer (PCa) we knocked out androgen receptor (AR) and H3.3 chaperones HIRA and DAXX in R1-AD1 (wild type AR) and R1-D567 (deltaLBD AR) cell lines. Integrative analysis with RNA-seq, ChIP-seq and ATAC-seq revealed that HIRA KO deregulates androgen-induced gene expression in PCa by reducing H3.3 incorporation, diminishing H3.3S31Ph and H3K27Ac, thus modifying recruitment of BRD4 and altering AR binding within enhancers of target genes.
2023-11-02 | GSE230741 | GEO
Project description:To study the function of histone variant H3.3 pathway in androgen receptor-driven transcription in prostate cancer (PCa) we knocked out androgen receptor (AR) and H3.3 chaperones HIRA and DAXX in R1-AD1 (wild type AR) and R1-D567 (deltaLBD AR) cell lines. Integrative analysis with RNA-seq, ChIP-seq and ATAC-seq revealed that HIRA KO deregulates androgen-induced gene expression in PCa by reducing H3.3 incorporation, diminishing H3.3S31Ph and H3K27Ac, thus modifying recruitment of BRD4 and altering AR binding within enhancers of target genes.
2023-11-02 | GSE230740 | GEO