Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

H3.3 nucleosome assembly mutants display a late-onset maternal effect

ABSTRACT: Maternally inherited RNA and protein control much of embryonic development. The impact of such maternal information beyond embryonic development is largely unclear. Here we report that maternal contribution of histone H3.3 assembly complexes can prevent the expression of late-onset anatomical, physiologic, and behavioral abnormalities of C. elegans. We show that mutants lacking hira-1, an evolutionarily conserved H3.3-deposition factor, have severe pleiotropic defects that manifest predominantly at adulthood. These late-onset defects can be maternally rescued, and maternally derived HIRA-1 protein can be detected in hira-1(-/-) progeny. A screen for mutants that mimic the hira-1 mutant phenotype identified a HIRA complex component (PQN-80/UBN1) and a second H3.3 chaperone (XNP-1/ATRX). pqn-80 and xnp-1 abnormalities are also maternally rescued. Furthermore, mutants lacking histone H3.3 have late-onset defects similar to those of hira-1, pqn-80, and xnp-1 mutants. These data demonstrate that H3.3 assembly complexes provide non-DNA-based heritable information that can markedly influence adult phenotype. We speculate that similar maternal effects might explain the missing heritability of 2 late-onset human diseases, such as Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE144686 | GEO | 2020/05/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

H3.3 nucleosome assembly mutants display a late-onset maternal effect

Project description:H3.3 nucleosome assembly mutants display a late-onset maternal effect

| PRJNA604584 | ENA

Histone chaperone ASF1 mediates H3.3-H4 deposition in Arabidopsis

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

Genome wide enrichment of H3.3 in WT and Hira-null embryonic stem cells and day 15 differentiated cardiac progenitor

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

Factors influencing in vivo deposition of histone variants H3.1 and H3.3

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

Genome-wide maps of chromatin state for H3.3 tagged cells

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

2013-04-18 | E-GEOD-45023 | biostudies-arrayexpress

Genome-wide maps of chromatin state for HIRA, UBN1 and ASF1a

2013-04-18 | E-GEOD-45024 | biostudies-arrayexpress

Expression data from Control and HIRA knockdown cells

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

Histone chaperone HIRA orchestrates H4K16ac-decorated dynamic chromatin in senescent cells and is required for suppression of oncogene-induced neoplasia.

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

Factors influencing in vivo deposition of histone variants H3.1 and H3.3

2011-12-16 | GSE31794 | GEO

RPA interacts with HIRA and regulates H3.3 deposition at gene regulatory elements in mammalian cells

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data