H3.3 nucleosome assembly mutants display a late-onset maternal effect
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA604584 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11005923.fastq.gz | Fastqsanger.gz | |||
| SRR11005924.fastq.gz | Fastqsanger.gz | |||
| SRR11005925.fastq.gz | Fastqsanger.gz | |||
| SRR11005926.fastq.gz | Fastqsanger.gz | |||
| SRR11005927.fastq.gz | Fastqsanger.gz |
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Project description: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.
2020-05-28 | GSE144686 | GEO
Project description:Maternally inherited RNA and proteins control much of embryonic development. The effect 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. Mitochondrial stress likely contributes to the late-onset defects, given that hira-1 mutants display mitochondrial stress, and the induction of mitochondrial stress results in at least some of the hira-1 late-onset abnormalities. A screen for mutants that mimic the hira-1 mutant phenotype identified PQN-80-a HIRA complex component, known as UBN1 in humans-and XNP-1-a second H3.3 chaperone, known as ATRX in humans. pqn-80 and xnp-1 abnormalities are also maternally rescued. Furthermore, mutants lacking histone H3.3 have a late-onset defect similar to a defect 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 late-onset human diseases, such as Alzheimer's disease, Parkinson's disease, and type 2 diabetes.
| S-EPMC7314652 | biostudies-literature
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
Project description:Histone variants and their chaperones are key regulators of eukaryotic transcription, and are critical for normal development. The histone variant H3.3 has been shown to play important roles in pluripotency and differentiation, and although its genome-wide patterns have been investigated, little is known about the role of its dynamic turnover in transcriptional regulation. To elucidate the role of H3.3 dynamics in embryonic stem cell (ESC) biology, we generated mouse ESC lines carrying a single copy of a doxycycline (Dox)-inducible HA-tagged version of H3.3, and monitored the rate of incorporation of the HA-tagged variant by ChIP-seq at varying time points following Dox induction. Active H3K4me3-enriched genes display high turnover dynamics in transcription start sites (TSS); H3K27me3-enriched genes have a lower turnover dynamics in the TSS, but higher turnover rates in gene bodies; developmental bivalent genes marked by both H3K4me3 and H3K27me3 show a mixed behavior with high TSS dynamics and high gene body dynamics, especially in genes bound by both PRC1 and PRC2. In contrast, genes proximal to super-enhancers show the most reduced gene-body turnover dynamics, while genes proximal to other enhancers show no unique pattern. In RA-treated cells, while the overall profile in expressed genes remains largely unaltered over the TSS and gene body, a significant and dramatic decrease in turnover occurs at the -1 nucleosome position immediately before the TSS, revealing a hyperdynamic nucleosome in promoters of genes expressed in ESCs. We suggest that histone turnover dynamics provides an additional mechanism involved in expression regulation, that gene-body turnover dynamics is distinct from that of promoter regions, and that a hyperdynamic -1 nucleosome marks promoters in ESCs. Our data provide evidence for regional regulation of H3.3 turnover in ESC promoters, and calls for testing, in high resolution, the dynamic behavior of additional histone variants and other structural chromatin proteins.
2017-09-05 | GSE88745 | GEO
Project description:Linker histones are involved in the formation of higher-order chromatin structure. Although linker histones have been implicated in the regulation of specific genes, it still remains unclear what their principal binding determinants are and how their repressive function in vitro can be reconciled with presumed broad binding in vivo. We generated a full genome, high resolution binding map of linker histone H1 in Drosophila Kc cells, using DamID. H1 binds at similar levels across much of the genome, both in classical euchromatin and heterochromatin. Strikingly, there are pronounced dips of low H1 occupancy around transcription start sites of active genes and at many distant cis-regulatory sites. H1 dips are not due to lack of nucleosomes. Rather, all regions with low binding of H1 show enrichment of the histone variant H3.3 which itself has been linked to high nucleosome turnover. Upon knockdown of H3.3, we find that H1 levels increase at sites previously not covered with H1 with a concomitant increase in nucleosome repeat length. These changes are independent of transcriptional changes. Our results show that the H3.3 protein counteracts association of H1 at genomic sites with high rates of histone turnover. This antagonism provides a mechanism to keep diverse genomic sites in an open chromatin conformation. For this study, we generated DamID profiles of histone H1 and RpII18 in Drosophila Kc167 cells. Additionally, we generated H1 profiles in cells treated with RNAi against white, H3.3B, or H3.3A and H3.3B. Nucleosome occupancy profiles were generated in untreated cells and cells treated with RNAi against white or H3.3A and H3.3B. Profiles of expression changes were generated for H3.3B RNAi and H3.3A and H3.3B RNAi. DamID experiments for H1 and RpII18 were performed in Drosophila cell cultures. Samples were hybridized to 380k NimbleGen arrays with 300 bp probe spacing. Formaldehyde-assisted isolation of regulatotry elements (FAIRE) was performed in Drosophila Kc167 cells. Samples were hybridized to 380k NimbleGen arrays with 300 bp probe spacing over non-crosslinked genomic DNA. Nucleosome positioning profiles were made by hybridizing mononucleosomal DNA over MNase digested purified genomic DNA on 380k NimbleGen arrays with 10 bp probe spacing. Expression profiles were made as H3.3 RNAi over white RNAi cohybridizations on spotted INDAC long oligo arrays. Every experiment was done in duplicate in the reverse dye orientation.
2010-06-23 | E-GEOD-16882 | biostudies-arrayexpress
Project description:Histone variants can effect nucleosome stability or affect histone of DNA modifications. H3.3 is a major H3 histone variant that is incorporated into chromatin outside of S-phase in various eukaryotes. In animals, H3.3 is associated with active transcription and possibly maintenance of transcriptional memory. Plant H3.3, which evolved independently of animal H3.3, is much less well understood. We performed ChIP-chip using chromatin from rosette leaves of 35S:H3.3-YFP plants.
2014-03-10 | E-MTAB-1685 | biostudies-arrayexpress
Project description:Linker histones are involved in the formation of higher-order chromatin structure. Although linker histones have been implicated in the regulation of specific genes, it still remains unclear what their principal binding determinants are and how their repressive function in vitro can be reconciled with presumed broad binding in vivo. We generated a full genome, high resolution binding map of linker histone H1 in Drosophila Kc cells, using DamID. H1 binds at similar levels across much of the genome, both in classical euchromatin and heterochromatin. Strikingly, there are pronounced dips of low H1 occupancy around transcription start sites of active genes and at many distant cis-regulatory sites. H1 dips are not due to lack of nucleosomes. Rather, all regions with low binding of H1 show enrichment of the histone variant H3.3 which itself has been linked to high nucleosome turnover. Upon knockdown of H3.3, we find that H1 levels increase at sites previously not covered with H1 with a concomitant increase in nucleosome repeat length. These changes are independent of transcriptional changes. Our results show that the H3.3 protein counteracts association of H1 at genomic sites with high rates of histone turnover. This antagonism provides a mechanism to keep diverse genomic sites in an open chromatin conformation. For this study, we generated DamID profiles of histone H1 and RpII18 in Drosophila Kc167 cells. Additionally, we generated H1 profiles in cells treated with RNAi against white, H3.3B, or H3.3A and H3.3B. Nucleosome occupancy profiles were generated in untreated cells and cells treated with RNAi against white or H3.3A and H3.3B. Profiles of expression changes were generated for H3.3B RNAi and H3.3A and H3.3B RNAi.
2009-10-15 | GSE16882 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE16882: Histone H1 binding is restricted by histone variant H3.3 (Nucleosome) GSE16883: Histone H1 binding is restricted by histone variant H3.3 (DamID) GSE16884: Histone H1 binding is restricted by histone variant H3.3 (Expression) GSE19764: Histone H1 binding is restricted by histone variant H3.3 (FAIRE) Refer to individual Series
2009-10-15 | E-GEOD-16885 | biostudies-arrayexpress
Project description:Using Tet-inhibited expression of epitope-tagged H3.3 combined with ChIP-Seq we undertook genome-wide measurements of H3.3 dissociation rates across the ESC genome and examined the relationship between H3.3-nucleosome turnover and ESC-specific transcription factors, chromatin modifiers and epigenetic marks.
2015-05-14 | GSE63641 | GEO
Project description:To understand how chromatin structure is organized by different histone variants, we have measured the genome-wide distribution of nucleosome core particles (NCPs) containing the histone variants H3.3 and H2A.Z in human cells. We find that a special class of NCPs containing both variants is enriched at ‘nucleosome-free regions’ of active promoters, enhancers and insulator regions. We show that preparative methods used previously in studying nucleosome structure result in the loss of these unstable double-variant NCPs. It seems likely that this instability facilitates the access of transcription factors to promoters and other regulatory sites in vivo. Other combinations of variants have different distributions, consistent with distinct roles for histone variants in the modulation of gene expression. genome-wide analysis of histone variants H2AZ, H3.3, and H3.3-H2A.Z double ChIP, plus input and genomic DNA controls in HeLa cells. H2A.Z samples are prepared under two different salt concentration conditions. (6 samples in total)
2009-07-26 | E-GEOD-13308 | biostudies-arrayexpress