Similar Datasets
Project description:Nucleosome occupancy profiles of 21-day old wild type (WT) and 3h1 Arabidopsis plants were generated by deep sequencing.
2019-07-10 | GSE113556 | GEO
Project description:Cellular senescence is a tumor-suppressing mechanism that is accompanied by characteristic chromatin condensation called senescence-associated heterochromatic foci (SAHFs). We found that individual SAHFs originate from individual chromosomes. SAHFs do not show alterations of posttranslational modifications of core histones that mark condensed chromatin in mitotic chromosomes, apoptotic chromatin, or transcriptionally inactive heterochromatin. Remarkably, SAHF-positive senescent cells lose linker histone H1 and exhibit increased levels of chromatin-bound high mobility group A2 (HMGA2). The expression of N-terminally enhanced green fluorescent protein (EGFP)-tagged histone H1 induces premature senescence phenotypes, including increased levels of phosphorylated p53, p21, and hypophosphorylated Rb, and a decrease in the chromatin-bound endogenous histone H1 level but not in p16 level accumulation or SAHF formation. However, the simultaneous ectopic expression of hemagglutinin-tagged HMGA2 and N-terminally EGFP-tagged histone H1 leads to significant SAHF formation (P < 0.001). It is known that histone H1 and HMG proteins compete for a common binding site, the linker DNA. These results suggest that SAHFs are a novel type of chromatin condensation involving alterations in linker DNA-binding proteins.
| S-EPMC2064697 | biostudies-literature
Project description:MNase analysis of linker histone H1 mutant
| PRJNA451507 | ENA
Project description:Transcriptiomic analysis of linker histone H1 mutant
| PRJNA451508 | ENA
Project description:To investigate the relationship between linker histone H1 and protein-protein interactions in the nucleolus, we used biochemical and proteomics approaches to characterize nucleoli purified from cultured human and mouse cells. Mass spectrometry identified 175 proteins in human T cell nucleolar extracts that bound to Sepharose-immobilized H1 in vitro. Gene ontology analysis found significant enrichment for H1 binding proteins with functions related to nucleolar chromatin structure and RNA polymerase I transcription regulation, rRNA processing, and mRNA splicing. Consistent with the affinity binding results, H1 existed in large (400 to >650kDa) macromolecular complexes in human T cell nucleolar extracts. To complement the biochemical experiments, we investigated the effects of in vivo H1 depletion on protein content and structural integrity of the nucleolus using the H1 triple isoform knockout (H1?TKO) mouse embryonic stem cell (mESC) model system. Proteomic profiling of purified wild-type mESC nucleoli identified a total of 613 proteins, only ~60% of which were detected in the H1 mutant nucleoli. Within the affected group, spectral counting analysis quantitated 135 specific nucleolar proteins whose levels were significantly altered in H1?TKO mESC. Importantly, the functions of the affected proteins in mESC closely overlapped with those of the human T cell nucleolar H1 binding proteins. Immunofluorescence microscopy of intact H1?TKO mESC demonstrated both a loss of nucleolar RNA content and altered nucleolar morphology resulting from in vivo H1 depletion. We conclude that H1 organizes and maintains an extensive protein-protein interaction network in the nucleolus required for nucleolar structure and integrity.
| S-EPMC4417401 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-07-09 | GSE113558 | GEO
Project description:Decoding the role of histone posttranslational modifications (PTMs) is key to understand the fundamental process of epigenetic regulation. This is well studied for PTMs of core histones but not for linker histone H1 in general and its ubiquitylation in particular due to a lack of proper tools. Here, we report on the chemical synthesis of site-specifically mono-ubiquitylated H1.2 and identify its ubiquitin-dependent interactome on a proteome-wide scale. We show that site-specific ubiquitylation of H1 at position K64 modulates interactions with deubiquitylating enzymes and the deacetylase SIRT1. Moreover, it affects H1-dependent chromatosome assembly and phase separation resulting in a more open chromatosome conformation generally associated with a transcriptionally active chromatin state. In summary, we propose that site-specific ubiquitylation plays a general regulatory role for linker histone H1.
| S-EPMC8190259 | biostudies-literature
Project description:Linker histone H1 is an essential regulatory protein for many critical biological processes, such as eukaryotic chromatin packaging and gene expression. Mis-regulation of H1s is commonly observed in tumor cells, where the balance between different H1 subtypes has been shown to alter the cancer phenotype. Consisting of a rigid globular domain and two highly charged terminal domains, H1 can bind to multiple sites on a nucleosomal particle to alter chromatin hierarchical condensation levels. In particular, the disordered H1 amino- and carboxyl-terminal domains (NTD/CTD) are believed to enhance this binding affinity, but their detailed dynamics and functions remain unclear. In this work, we used a coarse-grained computational model, AWSEM-DNA, to simulate the H1.0b-nucleosome complex, namely chromatosome. Our results demonstrate that H1 disordered domains restrict the dynamics and conformation of both globular H1 and linker DNA arms, resulting in a more compact and rigid chromatosome particle. Furthermore, we identified regions of H1 disordered domains that are tightly tethered to DNA near the entry-exit site. Overall, our study elucidates at near-atomic resolution the way the disordered linker histone H1 modulates nucleosome's structural preferences and conformational dynamics.
| S-EPMC9272445 | biostudies-literature
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 a 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.
| S-EPMC8113232 | biostudies-literature
Project description:Epigenetic silencing in mammals involves DNA methylation and posttranslational modifications of core histones. Here we show that the H1 linker histone plays a key role in regulating both DNA methylation and histone H3 methylation at the H19 and Gtl2 loci in mouse ES cells. Some, but not all, murine H1 subtypes interact with DNA methyltransferases DNMT1 and DNMT3B. The interactions are direct and require a portion of the H1 C-terminal domain. Expression of an H1 subtype that interacts with DNMT1 and DNMT3B in ES cells leads to their recruitment and DNA methylation of the H19 and Gtl2 imprinting control regions. H1 also interferes with binding of the SET7/9 histone methyltransferase to the imprinting control regions, inhibiting production of an activating methylation mark on histone H3 lysine 4. H1-dependent recruitment of DNMT1 and DNMT3B and interference with the binding of SET7/9 also were observed with chromatin reconstituted in vitro. The data support a model in which H1 plays an active role in helping direct two processes that lead to the formation of epigenetic silencing marks. The data also provide evidence for functional differences among the H1 subtypes expressed in somatic mammalian cells.
| S-EPMC3562819 | biostudies-literature