Effect of a cardiomyocyte-specific Hira conditional knockout on gene expression in the heart
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71833 | GEO | 2016/04/06
SECONDARY ACCESSION(S): PRJNA292296
REPOSITORIES: GEO
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Project description:We performed gene expression profiling by microarray using RNA extracted from healthy free wall left ventricle tissues from control and Hira cardiomyocyte-specific conditional knockout mice at 6 weeks of age. Hira is a histone chaperone responsible for replication-independent incorporation of histone variant H3.3 at actively transcribed regions. Conditional knockout of Hira in cardiomyocytes resulted in impaired cardiac function, cardiomyocyte degeneration and focal replacement fibrosis. These results illustrate the role of Hira in controlling the cardiac gene program. 4 animals per group (control and Hira conditional knockout) hybridized in triplicate. RNA was extracted from healthy free wall left ventricle.
2016-04-06 | E-GEOD-71833 | biostudies-arrayexpress
Project description:We performed gene expression profiling by microarray using RNA extracted from the tibialis anterior of control and Hira myofiber-specific conditional knockout mice at 6 months of age. Hira is a histone chaperone responsible for replication-independent incorporation of histone variant H3.3 at actively transcribed loci. Conditional knockout of Hira in myofibers improved strength and endurance, caused hypertrophy and regeneration, and increased the percentage of type I fibers. These results illustrate the physiological consequences of disrupting Hira-mediated chromatin assembly in myofibers.
2017-06-26 | GSE90900 | GEO
Project description:HIRA is a histone chaperone that modulates gene expression through the deposition of H3.3. Conditional knockout of Hira in embryonic mouse hearts leads to cardiac septal defects. However, the effects of HIRA on the gene expression profile at earlier stages of cardiogenic mesoderm differentiation has not yet been studied. Differentiation of mouse embryonic stem cells (mESCs) towards cardiomyocytes mimics some of these events and is an accepted model of these early stages. We performed RNA-Seq and H3.3-HA ChIP-seq on both WT and Hira-null mESCs and early cardiomyocyte progenitors of both genotypes. Analysis of our RNA-seq data showed differential down regulation of cardiovascular development-related genes in Hira-null cardiomyocytes compared to WT cardiomyocytes. Correlating these data with H3.3 enrichment showed that HIRA is required for the expression of the transcription factors (TFs) Gata6, Meis1 and Tbx2. These TFs displayed diminished HIRA-dependent H3.3 enrichment in their gene bodies or at their transcription start site in the absence of HIRA. Our results reveal new transcription factors through which HIRA influences cardiogenesis in vitro and potentially in vivo.
2019-01-18 | GSE112078 | GEO
Project description:We performed gene expression profiling by microarray using RNA extracted from the tibialis anterior of control and Hira myofiber-specific conditional knockout mice at 6 weeks of age. Hira is a histone chaperone responsible for replication-independent incorporation of histone variant H3.3 at actively transcribed loci. Conditional knockout of Hira in myofibers caused hypertrophy, degeneration, and increased the percentage of type I fibers. These results illustrate the physiological consequences of disrupting Hira-mediated chromatin assembly in myofibers.
2017-06-26 | GSE97359 | GEO
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 HIRA chaperone complex, comprised of HIRA, UBN1 and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand its function and mechanism, we integrated HIRA, UBN1, ASF1a and histone H3.3 ChIP-seq and gene expression analyses. Most HIRA-binding sites co-localize with UBN1, ASF1a and H3.3 at active promoters and active and weak/poised enhancers. At promoters, binding of HIRA/UBN1/ASF1a correlates with the level of gene expression. HIRA is required for deposition of histone H3.3 at its binding sites. There are marked differences in nucleosome and co-regulator composition at different classes of HIRA-bound regulatory site. Underscoring this, we report novel physical interactions between the HIRA complex and transcription factors, a chromatin insulator and an ATP-dependent chromatin-remodelling complex. Our results map the distribution of the HIRA chaperone across the chromatin landscape and point to different interacting partners at functionally distinct regulatory sites. We used microarrays to detail the global programme of gene expression after knockdown of HIRA HeLa cells were nucleofacted with Dharmacon control siRNA and siRNA to HIRA and RNA was isolated 72 hours after transfection in four biological replicates
2013-04-18 | E-GEOD-45022 | biostudies-arrayexpress
Project description:The HIRA chaperone complex, comprised of HIRA, UBN1 and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand its function and mechanism, we integrated HIRA, UBN1, ASF1a and histone H3.3 ChIP-seq and gene expression analyses. Most HIRA-binding sites co-localize with UBN1, ASF1a and H3.3 at active promoters and active and weak/poised enhancers. At promoters, binding of HIRA/UBN1/ASF1a correlates with the level of gene expression. HIRA is required for deposition of histone H3.3 at its binding sites. There are marked differences in nucleosome and co-regulator composition at different classes of HIRA-bound regulatory site. Underscoring this, we report novel physical interactions between the HIRA complex and transcription factors, a chromatin insulator and an ATP-dependent chromatin-remodelling complex. Our results map the distribution of the HIRA chaperone across the chromatin landscape and point to different interacting partners at functionally distinct regulatory sites. Examination of 3 histone chaperone proteins in HeLa cells
2013-04-18 | E-GEOD-45024 | biostudies-arrayexpress
Project description:The HIRA chaperone complex, comprised of HIRA, UBN1 and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand its function and mechanism, we integrated HIRA, UBN1, ASF1a and histone H3.3 ChIP-seq and gene expression analyses. Most HIRA-binding sites co-localize with UBN1, ASF1a and H3.3 at active promoters and active and weak/poised enhancers. At promoters, binding of HIRA/UBN1/ASF1a correlates with the level of gene expression. HIRA is required for deposition of histone H3.3 at its binding sites. There are marked differences in nucleosome and co-regulator composition at different classes of HIRA-bound regulatory site. Underscoring this, we report novel physical interactions between the HIRA complex and transcription factors, a chromatin insulator and an ATP-dependent chromatin-remodelling complex. Our results map the distribution of the HIRA chaperone across the chromatin landscape and point to different interacting partners at functionally distinct regulatory sites. We used microarrays to detail the global programme of gene expression after knockdown of HIRA
2013-04-18 | GSE45022 | GEO
Project description:The HIRA chaperone complex, comprised of HIRA, UBN1 and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand its function and mechanism, we integrated HIRA, UBN1, ASF1a and histone H3.3 ChIP-seq and gene expression analyses. Most HIRA-binding sites co-localize with UBN1, ASF1a and H3.3 at active promoters and active and weak/poised enhancers. At promoters, binding of HIRA/UBN1/ASF1a correlates with the level of gene expression. HIRA is required for deposition of histone H3.3 at its binding sites. There are marked differences in nucleosome and co-regulator composition at different classes of HIRA-bound regulatory site. Underscoring this, we report novel physical interactions between the HIRA complex and transcription factors, a chromatin insulator and an ATP-dependent chromatin-remodelling complex. Our results map the distribution of the HIRA chaperone across the chromatin landscape and point to different interacting partners at functionally distinct regulatory sites.
2013-04-18 | GSE45024 | 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 | GSE161054 | GEO