Genome-wide maps of chromatin state for HIRA, UBN1 and ASF1a
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Tony McBryan
PROVIDER: E-GEOD-45024 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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 H3.3 histone modification in HeLA cells with accompanying FAIRE data
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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: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.
2013-04-18 | GSE45024 | 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 | GSE45023 | 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
2013-04-18 | GSE45022 | GEO
Project description:The mammalian HIRA/UBN1/ASF1a complex is a histone chaperone complex that is conserved from yeast (Saccharomyces cerevisiae) to humans. This complex preferentially deposits the histone variant H3.3 into chromatin in a DNA replication-independent manner and is implicated in diverse chromatin regu- latory events from gene activation to heterochromatinization. In yeast, the orthologous complex consists of three Hir proteins (Hir1p, Hir2p, and Hir3p), Hpc2p, and Asf1p. Yeast Hir3p has weak homology to CABIN1, a fourth member of the human complex, suggesting that Hir3p and CABIN1 may be orthologs. Here we show that HIRA and CABIN1 interact at ectopic and endogenous levels of expression in cells, and we isolate the quaternary HIRA/UBN1/CABIN1/ASF1a (HUCA) complex, assembled from recombinant proteins. Mutational analyses support the view that HIRA acts as a scaffold to bring together UBN1, ASF1a, and CABIN1 into a quaternary complex. We show that, like HIRA, UBN1, and ASF1a, CABIN1 is involved in heterochromatinization of the genome of senescent human cells. Moreover, in proliferating cells, HIRA and CABIN1 regulate overlapping sets of genes, and these genes are enriched in the histone variant H3.3. In sum, these data demonstrate that CABIN1 is a functional member of the human HUCA complex and so is the likely ortholog of yeast Hir3p. We used microarrays to detail the global programme of gene expression after knockdown of HIRA and CABIN1 in 3 replicates HeLa cells were nucleofacted with Dharmacon control siRNA and siRNA to HIRA and CABIN1 and RNA was isolated 72 hours after transfection.
2013-03-20 | E-GEOD-45295 | biostudies-arrayexpress
Project description:The mammalian HIRA/UBN1/ASF1a complex is a histone chaperone complex that is conserved from yeast (Saccharomyces cerevisiae) to humans. This complex preferentially deposits the histone variant H3.3 into chromatin in a DNA replication-independent manner and is implicated in diverse chromatin regu- latory events from gene activation to heterochromatinization. In yeast, the orthologous complex consists of three Hir proteins (Hir1p, Hir2p, and Hir3p), Hpc2p, and Asf1p. Yeast Hir3p has weak homology to CABIN1, a fourth member of the human complex, suggesting that Hir3p and CABIN1 may be orthologs. Here we show that HIRA and CABIN1 interact at ectopic and endogenous levels of expression in cells, and we isolate the quaternary HIRA/UBN1/CABIN1/ASF1a (HUCA) complex, assembled from recombinant proteins. Mutational analyses support the view that HIRA acts as a scaffold to bring together UBN1, ASF1a, and CABIN1 into a quaternary complex. We show that, like HIRA, UBN1, and ASF1a, CABIN1 is involved in heterochromatinization of the genome of senescent human cells. Moreover, in proliferating cells, HIRA and CABIN1 regulate overlapping sets of genes, and these genes are enriched in the histone variant H3.3. In sum, these data demonstrate that CABIN1 is a functional member of the human HUCA complex and so is the likely ortholog of yeast Hir3p. We used microarrays to detail the global programme of gene expression after knockdown of HIRA and CABIN1 in 3 replicates
2013-03-20 | GSE45295 | GEO
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).
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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.
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