HIRA null vs parental mES cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19542 | GEO | 2009/12/19
SECONDARY ACCESSION(S): PRJNA122321
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: The goals of this study are to compare transcriptome profiling (RNA-seq) resulting from the knockout of Hira in undifferentiated mouse embryonic stem cells (mESCs) and in day 15 differentiated cardiomyocytes.Methods: RNA extraction was done in duplicate from WT and Hira-null mESCs at day0 and day15 using TRIzol reagent. RNAseq was done onIllumina Nextseq500 and processed by the ICH genomics facility, reads were aligned and normalised using BOWTIE and DEseq R2 package. Gene lists were filtered using adjusted p-value ≤ 0.05 and absolute fold change ≥ 2. Results:We identified 1680 transcripts changed in the absence of HIRA in day 15 differentiated cardiomyocytes. GO term cardiovascular system development was the most downregulated gene set(p-value ≤ 0.01 and FDR ≤0.1. Conclusion: this study analysis the role of HIRA in early cardiac mesoderm development usinf an invitro mESCs model.
2019-04-01 | GSE111910 | GEO
Project description:WT and Hira-null undifferentiated mESCs and day15 differentiated cardiomyocytes
| PRJNA438521 | ENA
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:The assembly of nucleosomes by histone chaperones is an important component of transcriptional regulation. Here we have assessed the global roles of the S. pombe HIRA histone chaperone complex. Microarray analysis indicates that inactivation of the HIRA complex results in increased expression of at least 4% of fission yeast genes. HIRA-regulated genes overlap with those which are normally repressed in vegetatively growing cells, such as targets of the Clr6 histone deacetylase and silenced genes located in subtelomeric regions. HIRA is also required for silencing of all 13 intact copies of the Tf2 long terminal repeat (LTR) retrotransposon. However, the role of HIRA is not restricted to bona fide promoters, because it also suppresses non-coding transcripts from solo LTR elements and spurious antisense transcripts from cryptic promoters associated with transcribed regions. Furthermore, the HIRA complex is essential in the absence of the quality control provided by nuclear exosome-mediated degradation of illegitimate transcripts. This suggests that HIRA restricts genomic accessibility, and, consistent with this, the chromosomes of cells lacking HIRA are more susceptible to genotoxic agents that cause double strand breaks. Thus the HIRA histone chaperone is required to maintain the protective functions of chromatin.
2009-07-22 | E-MTAB-130 | biostudies-arrayexpress
Project description:The synthesis of poly(ADP-ribose) (PAR) reconfigures the local environment and recruits repair complexes to damaged chromatin. The degradation of PAR by PARG is essential for progression and completion of DNA repair. Here, we show that inhibition of PARG disrupts homology-directed repair (HDR) mechanisms that underpin alternative telomere lengthening (ALT). By proteomics, we uncovered a novel role for PARylation in regulating the chromatin assembly factor, HIRA in ALT cancer cells. We show that HIRA is enriched at telomeres during G2 phase and is indispensable for histone H3.3 deposition and telomere DNA synthesis. Depletion of HIRA elicits systemic death of ALT cancer cells was mitigated by re-expression of ATRX protein that is frequently inactivated in ALT tumors. We propose that PARylation enables HIRA to fulfill its essential role in the adaptive response due to ATRX deficiency that pervades ALT cancers.
2020-10-12 | PXD020243 | Pride
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:Plant development is characterised by the capacity to reprogram differentiated cells to initiate asexual reproduction and to produce new organs such as lateral roots. To test whether HIRA could be involved in aspects of developmental reprogramming we studied the effect of HIRA during de-differentiation Arabidopsis root tissue was digested with enzyme to generate protoplast. This process would induce plant cell dedifferentiation. Experiments were performed in WT and hira background to understand how hira affect plant dedifferentiation process.
2014-10-01 | E-GEOD-57044 | 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 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. We used microarrays to detail the global programme of gene expression after knockdown of HIRA
2013-04-18 | GSE45022 | GEO