Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin
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ABSTRACT:
PROVIDER: PRJNA387003 | ENA |
REPOSITORIES: ENA
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Project description: Not available
| S-EPMC5561251 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-08-18 | GSE99016 | GEO
Project description:Genome wide distribution of R-loops in Wild Type and RNAi dH1 Drosophila melanogaster S2 cells
2017-08-18 | GSE99014 | GEO
Project description:Genome wide distribution of gammaH2AvD in Wild Type and RNAi dH1 Drosophila melanogaster S2 cells
2017-08-18 | GSE99004 | GEO
Project description:Drosophila dosage compensation is an epigenetic phenomenon in which the transcription of most genes on X-chromosome is enhanced by approximately two folds in males to equalize that in females. In this study, we provide evidence that transcriptional repressors, such as HP1 and linker histone H1, are globally reduced on male X chromosome. We further investigated the role of HP1 and linker H1 on X chromosome dosage compensation using flies with overexpression of HP1 and H1, we demonstrate that these repressors surpress H4K16 acetylation, presence of the elongating RNA Pol II and the transcription of the genes on male X chromosomes. To understand how H1 and HP1 are regulated on male X chromosome, we next explored the relationship between MOF and the two repressors of chromatin. We show that the hyperacetylation of H4K16 induced by MOF resulted in the loss of H1 and HP1 on chromatin and global chromatin decondensation. Our biochemical analysis further shows that the presence of acetylation on histone H4 at lysine 16 directly inhibits the interaction between histone H4 and linker H1. This study therefore provides novel clues on understanding the dynamic regulation of chromatin regulators on male X chromosome dosage compensation.
2017-11-01 | GSE29537 | GEO
Project description:In flowering plants, heterochromatin is demarcated by the histone variant H2A.W, elevated levels of the linker histone H1, and specific epigenetic modifications, such as high levels of DNA methylation at both CG and non-CG sites. How H2A.W regulates heterochromatin organization and interacts with other heterochromatic features is unclear. Here, we create an h2a.w null mutant via CRISPR-Cas9, h2a.w-2, to analyze the in vivo function of H2A.W. We find that H2A.W antagonizes deposition of H1 at heterochromatin and that non-CG methylation and accessibility are moderately decreased in h2a.w-2 heterochromatin. Compared to H1 loss alone, combined loss of H1 and H2A.W greatly increases accessibility and facilitates non-CG DNA methylation in heterochromatin, suggesting co-regulation of heterochromatic features by H2A.W and H1. Our results suggest that H2A.W helps maintain optimal heterochromatin accessibility and DNA methylation by promoting chromatin compaction together with H1, while also inhibiting excessive H1 incorporation.
2021-03-26 | GSE146948 | GEO
Project description:Linker histone H1 plays a key role in chromatin organization and maintenance, however, our knowledge of the regulation of H1 functions by its posttranslational modifications (PTMs) is very limited. In this study, we report on the generation of homogeneously and site-specifically mono- and di-acetylated H1 (H1 Ac) using genetic code expansion. We used these modified histones to identify and comprehensively characterize the acetylation-dependent cellular interactome for linker histone H1 and show that site-specific acetylation results in overlapping, but distinct groups of interacting partners. Intriguingly, H1 acetylation-specific interactors comprise translational initiation factors and are involved in transcriptional regulation, suggesting that acetylation of H1 may indeed act as a regulator of the linker histone H1 by modulation of protein-protein interactions.
2021-07-09 | PXD025832 | Pride
Project description:Chromosomal RNAs (cRNAs) are a poorly understood fraction of cellular RNAs that co-purify with chromatin. Here we show that, in Drosophila, cRNAs constitute a heterogeneous group of RNA species that cover ~28% of the genome. Intriguingly, we found that cRNAs are highly enriched in heterochromatic transcripts. Our results show that heterochromatic cRNAs interact with the hnRNP A/B proteins hrp36 and hrp48 to assemble into RNP particles. We also show that depletion of linker histone dH1, a major component of chromatin, impairs assembly of hrp36 and hrp48 onto heterochromatic cRNAs. Concomitantly, impaired cRNAs assembly induces the accumulation of heterochromatic cRNAs and the formation of unscheduled RNA::DNA hybrids (R-loops). Linker histones H1 are known to regulate chromatin structure and compaction and, indeed, we show that dH1 depletion perturbs chromatin organization, reducing nucleosome occupancy and specifically increasing accessibility and 3D interactions within heterochromatin. These perturbations facilitate annealing of cRNAs to the DNA template, enhancing R-loops formation and cRNAs retention at heterochromatin. Altogether, these results unveil the unexpected contribution of linker histones to RNPs assembly and homeostasis of cRNAs.
2024-04-23 | GSE228076 | GEO
Project description:Chromosomal RNAs (cRNAs) are a poorly understood fraction of cellular RNAs that co-purify with chromatin. Here we show that, in Drosophila, cRNAs constitute a heterogeneous group of RNA species that cover ~28% of the genome. Intriguingly, we found that cRNAs are highly enriched in heterochromatic transcripts. Our results show that heterochromatic cRNAs interact with the hnRNP A/B proteins hrp36 and hrp48 to assemble into RNP particles. We also show that depletion of linker histone dH1, a major component of chromatin, impairs assembly of hrp36 and hrp48 onto heterochromatic cRNAs. Concomitantly, impaired cRNAs assembly induces the accumulation of heterochromatic cRNAs and the formation of unscheduled RNA::DNA hybrids (R-loops). Linker histones H1 are known to regulate chromatin structure and compaction and, indeed, we show that dH1 depletion perturbs chromatin organization, reducing nucleosome occupancy and specifically increasing accessibility and 3D interactions within heterochromatin. These perturbations facilitate annealing of cRNAs to the DNA template, enhancing R-loops formation and cRNAs retention at heterochromatin. Altogether, these results unveil the unexpected contribution of linker histones to RNPs assembly and homeostasis of cRNAs.
2024-04-23 | GSE228140 | GEO
Project description:Chromosomal RNAs (cRNAs) are a poorly understood fraction of cellular RNAs that co-purify with chromatin. Here we show that, in Drosophila, cRNAs constitute a heterogeneous group of RNA species that cover ~28% of the genome. Intriguingly, we found that cRNAs are highly enriched in heterochromatic transcripts. Our results show that heterochromatic cRNAs interact with the hnRNP A/B proteins hrp36 and hrp48 to assemble into RNP particles. We also show that depletion of linker histone dH1, a major component of chromatin, impairs assembly of hrp36 and hrp48 onto heterochromatic cRNAs. Concomitantly, impaired cRNAs assembly induces the accumulation of heterochromatic cRNAs and the formation of unscheduled RNA::DNA hybrids (R-loops). Linker histones H1 are known to regulate chromatin structure and compaction and, indeed, we show that dH1 depletion perturbs chromatin organization, reducing nucleosome occupancy and specifically increasing accessibility and 3D interactions within heterochromatin. These perturbations facilitate annealing of cRNAs to the DNA template, enhancing R-loops formation and cRNAs retention at heterochromatin. Altogether, these results unveil the unexpected contribution of linker histones to RNPs assembly and homeostasis of cRNAs.
2024-04-23 | GSE249374 | GEO