Genome-wide maps of linker histone H1 lysine 85 acetylation in HCT116 cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE113238 | GEO | 2018/04/18
REPOSITORIES: GEO
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Project description:Genome-wide maps of linker histone H1 lysine 85 acetylation in HCT116 cells
| PRJNA450529 | ENA
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: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:Both, acetylation of histones and of histone variant H2A.Z are conserved features of eukaryotic transcription start sites (TSSs) and both features appear to be critical for correct transcription initiation. However, complex patterns of transcriptional regulation have complicated the establishment of functional links between histone acetylation, H2A.Z deposition and their importance in transcription regulation. To elucidate these links, we took advantage of the unusual genome organization in Trypanosoma brucei, a highly divergent eukaryote. In T. brucei genes are organized in long polycistronic transcription units, drastically reducing the sites of transcription initiation. Employing a highly sensitive and quantitative mass-spectrometry-based approach, we quantified the genome-wide histone acetylation and methylation pattern and identified various acetyl and methyl marks exclusively enriched at TSSs In addition, we show that deletion of histone acetyltransferase 2 results in a loss of H4 acetylation at TSSs, a loss of H2A.Z deposition at TSSs and a shift in the sites of transcription initiation. Combined, our findings demonstrate an evolutionary conserved link between histone H4 acetylation, H2A.Z deposition and RNA transcription initiation.
2020-03-24 | PXD014452 | Pride
Project description:We employed the DamID technique to systematically map the genomic distribution of all canonical somatic H1 subtypes (H1.1-H1.5) in human IMR90 cells. Human cells contain up to eleven histone H1 proteins, with different spatial and temporal expression patterns. These include five canonical, replication-dependent somatic H1 subtypes (H1.1, H1.2, H1.3, H1.4 and H1.5). Despite being a key chromatin component, the genomic distribution of the somatic canonical H1 subtypes is still unknown and their role in chromatin related processes has so far remained elusive. Here we employed a DamID approach to map for the first time the genomic localization of all somatic canonical H1 subtypes in human cells. Our integrative analysis reveals novel insights into H1 subtype distribution and uncovers functional chromatin features potentially regulating the H1 genomic landscape. In general H1.2 to H1.5 are depleted from GC-rich regions and regulatory regions associated with active transcription. H1.1 shows a binding profile distinct from the other subtypes, suggesting a unique function for H1.1 in chromatin-regulated processes. Interestingly, our data indicate a novel role for somatic H1 subtypes in the three-dimensional organization of the genome by marking repressive regions within topological domains such as LADs. Our work integrates the five somatic linker histone H1 subtypes into the epigenome maps of human cells and provides a resource to refine our understanding of the significance of H1 and its heterogeneity in the control of genome function. DamID profiling of somatic linker histone variants H1.1, H1.2, H1.3, H1.4 and H1.5 in human fibroblasts. Two biological replicate samples of all H1 variants were hybridized on NimbleGen Human ChIP-chip 2.1M Economy Whole-Genome Tiling - Array GPL16055 covering small human chromosomes.
2013-06-15 | E-GEOD-40886 | biostudies-arrayexpress
Project description:At least six histone H1 variants exist in mammalian somatic cells that bind to the linker DNA and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition, H1 seems to be involved in the active regulation of gene expression. It is not well known whether the different variants have specific roles, are distributed differentially along the genome, or regulate specific promoters. By taking advantage of specific antibodies to H1 variants and HA-tagged recombinant H1 variants expressed in a breast cancer-derived cell line, we have investigated the distribution of the different somatic H1 variants (H1.2 to H1.5, H1.0 and H1X) in particular promoters and genome-wide. Analysis of H1 (H1.0, H1.2, H1.3, H1.4, H1.5 and H1X) and H3 abundance in promoter regions
2014-02-04 | E-GEOD-49333 | biostudies-arrayexpress
Project description:We employed the DamID technique to systematically map the genomic distribution of all canonical somatic H1 subtypes (H1.1-H1.5) in human IMR90 cells. Human cells contain up to eleven histone H1 proteins, with different spatial and temporal expression patterns. These include five canonical, replication-dependent somatic H1 subtypes (H1.1, H1.2, H1.3, H1.4 and H1.5). Despite being a key chromatin component, the genomic distribution of the somatic canonical H1 subtypes is still unknown and their role in chromatin related processes has so far remained elusive. Here we employed a DamID approach to map for the first time the genomic localization of all somatic canonical H1 subtypes in human cells. Our integrative analysis reveals novel insights into H1 subtype distribution and uncovers functional chromatin features potentially regulating the H1 genomic landscape. In general H1.2 to H1.5 are depleted from GC-rich regions and regulatory regions associated with active transcription. H1.1 shows a binding profile distinct from the other subtypes, suggesting a unique function for H1.1 in chromatin-regulated processes. Interestingly, our data indicate a novel role for somatic H1 subtypes in the three-dimensional organization of the genome by marking repressive regions within topological domains such as LADs. Our work integrates the five somatic linker histone H1 subtypes into the epigenome maps of human cells and provides a resource to refine our understanding of the significance of H1 and its heterogeneity in the control of genome function.
2013-06-15 | GSE40886 | GEO
Project description:Post-translational modifications (PTMs) of histones have fundamental effects on chromatin structure and function. While the impact of PTMs on the function of core histones are increasingly well understood, this is much less the case for modifications of linker histone H1, which is at least in part due to a lack of proper tools. In this work, we establish the assembly of intact chromatosomes containing site-specifically ubiquitylated and acetylated linker histone H1.2 variants obtained by a combination of chemical biology approaches. We then use these complexes in a tailored affinity enrichment mass spectrometry workflow to identify and comprehensively characterize chromatosome-specific cellular interactomes and the impact of site-specific linker histone modifications on a proteome-wide scale. We validate and benchmark our approach by western-blotting and by confirming the involvement of chromatin-bound H1.2 in the recruitment of proteins involved in DNA double-strand break repair using an in vitro ligation assay. We relate our data to previous work and in particular compare it to data on modification-specific interaction partners of free H1. Taken together, our data supports the role of chromatin-bound H1 as a regulatory protein with distinct functions beyond DNA compaction and constitutes an important resource for future investigations of histone epigenetic modifications.
2023-11-02 | PXD040236 | Pride
Project description:Linker histone H1 has been correlated with transcriptional inhibition, but the mechanistic basis of the inhibition and its reversal during gene activation has remained enigmatic. We report that H1-compacted chromatin, reconstituted in vitro, blocks transcription by abrogating core histone modifications by p300 but not activator and p300 binding. Transcription from H1-bound chromatin is elicited by H1 chaperone NAP1, which is recruited in a gene-specific manner through direct interactions with activator-bound p300 that facilitate core histone acetylation (by p300) and concomitant eviction of H1 and H2A/H2B. An analysis in B cells confirms the strong dependency on NAP1-mediated H1 eviction for induction of the silent CD40 gene and further demonstrates that H1 eviction, seeded by activator-p300-NAP1 interactions, is propagated over a CTCF-demarcated region through a distinct mechanism that also involves NAP1. Our results confirm direct transcriptional inhibition by H1 and establish a gene-specific H1 eviction mechanism through an activator-p300-NAP1-H1 pathway.
2019-02-06 | GSE126083 | GEO
Project description:Newly discovered histone lysine acylations increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters, where acetylation guides the binding of Brdt, a bromodomain-and-extra-terminal protein, thereby mediating stage-specific gene expression programs. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbour competing histone acetylation and butyrylation marks at H4 K5 and K8. Histone butyrylation, despite acting as a direct stimulator of transcription, competes with acetylation, especially at H4 K5, to prevent Brdt binding. The observed in vivo H4 K5K8 acetylation butyrylation state at active promoters is reproduced in vitro where p300 indistinctly acetylates and butyrylates H4 K5 and K8. Altogether, highly active gene promoter regions are characterized by alternating H4 acetylation and butyrylation sustaining direct gene activation and a dynamic bromodomain binding.
2016-07-13 | GSE77277 | GEO