scholarly journals Loss of linker histone H1 in cellular senescence

2006 ◽  
Vol 175 (6) ◽  
pp. 869-880 ◽  
Author(s):  
Ryo Funayama ◽  
Motoki Saito ◽  
Hiroko Tanobe ◽  
Fuyuki Ishikawa
Keyword(s):  
Cellular Senescence ◽  
Fluorescent Protein ◽  
Chromatin Condensation ◽  
Ectopic Expression ◽  
High Mobility ◽  
Histone H1 ◽  
Linker Histone ◽  
Hmg Proteins ◽  
Mitotic Chromosomes ◽  
Linker Histone H1

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.

scholarly journals Yeast HMO1: Linker Histone Reinvented

2016 ◽  
Vol 81 (1) ◽  
Author(s):  
Arvind Panday ◽  
Anne Grove
Keyword(s):  
Ribosomal Proteins ◽  
High Mobility ◽  
Histone H1 ◽  
Strand Break ◽  
Linker Histone ◽  
Content Type ◽  
Linker Histone H1 ◽  
Nucleosome Core ◽  
Rich Domain ◽  
Nucleosome Density

SUMMARY Eukaryotic genomes are packaged in chromatin. The higher-order organization of nucleosome core particles is controlled by the association of the intervening linker DNA with either the linker histone H1 or high mobility group box (HMGB) proteins. While H1 is thought to stabilize the nucleosome by preventing DNA unwrapping, the DNA bending imposed by HMGB may propagate to the nucleosome to destabilize chromatin. For metazoan H1, chromatin compaction requires its lysine-rich C-terminal domain, a domain that is buried between globular domains in the previously characterized yeast Saccharomyces cerevisiae linker histone Hho1p. Here, we discuss the functions of S. cerevisiae HMO1, an HMGB family protein unique in containing a terminal lysine-rich domain and in stabilizing genomic DNA. On ribosomal DNA (rDNA) and genes encoding ribosomal proteins, HMO1 appears to exert its role primarily by stabilizing nucleosome-free regions or “fragile” nucleosomes. During replication, HMO1 likewise appears to ensure low nucleosome density at DNA junctions associated with the DNA damage response or the need for topoisomerases to resolve catenanes. Notably, HMO1 shares with the mammalian linker histone H1 the ability to stabilize chromatin, as evidenced by the absence of HMO1 creating a more dynamic chromatin environment that is more sensitive to nuclease digestion and in which chromatin-remodeling events associated with DNA double-strand break repair occur faster; such chromatin stabilization requires the lysine-rich extension of HMO1. Thus, HMO1 appears to have evolved a unique linker histone-like function involving the ability to stabilize both conventional nucleosome arrays as well as DNA regions characterized by low nucleosome density or the presence of noncanonical nucleosomes.

SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity

2021 ◽  
Author(s):  
Daoud Sheban ◽  
Tom Shani ◽  
Roey Maor ◽  
Alejandro Aguilera-Castrejon ◽  
Nofar Mor ◽  
...  
Keyword(s):  
Cell Fate ◽  
Chromatin Condensation ◽  
Histone H1 ◽  
Embryonic Cell ◽  
Linker Histone ◽  
Linker Histone H1

scholarly journals Structural organization of DNA–protein complexes of chromatin studied by vibrational and electronic circular dichroism

2010 ◽  
Vol 24 (3-4) ◽  
pp. 239-244 ◽  
Author(s):  
Alexander Polyanichko ◽  
Helmut Wieser
Keyword(s):  
Circular Dichroism ◽  
Protein Complexes ◽  
High Mobility ◽  
Histone H1 ◽  
Cd Spectroscopy ◽  
Linker Histone ◽  
High Mobility Group ◽  
Ir Absorption ◽  
Linker Histone H1 ◽  
Circular Dichroïsm

Structure and functioning of chromatin is determined by interactions of DNA with numerous nuclear proteins. The most abundant and yet not completely understood non-histone chromosomal proteins are those belonging to a High Mobility Group (HMG) namely HMGB1. The interplay of this protein on DNA with linker histone H1 and other proteins determines both structure and functioning of the chromatin. A combination of UV and IR absorption and circular dichroism (CD) spectroscopy was applied to investigate the structure and formation of large supramolecular DNA–protein complexes. This combination of techniques was used to overcome limitations of UV-CD (ECD) spectroscopy due to considerable light scattering in such solutions. Based on the analysis of FTIR and UV circular dichroism spectra and AFM imaging the interaction of DNA with high-mobility group non-histone chromatin protein HMGB1 and linker histone H1 was studied.

scholarly journals Chromatin-Specific Remodeling by HMGB1 and Linker Histone H1 Silences Proinflammatory Genes during Endotoxin Tolerance

2009 ◽  
Vol 29 (7) ◽  
pp. 1959-1971 ◽  
Author(s):  
Mohamed El Gazzar ◽  
Barbara K. Yoza ◽  
Xiaoping Chen ◽  
Benjamin A. Garcia ◽  
Nicolas L. Young ◽  
...  
Keyword(s):  
High Mobility ◽  
Histone H1 ◽  
Linker Histone ◽  
Mrna Levels ◽  
Transcription Activator ◽  
Blood Leukocytes ◽  
Necrosis Factor Alpha ◽  
Linker Histone H1 ◽  
Tnf Α ◽  
H3k9 Dimethylation

ABSTRACT Epigenetic silencing of tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) transcription occurs in blood leukocytes of animals and humans after the initiation of severe systemic inflammation (SSI). We previously reported that the epigenetic signature requires induction of NF-κB factor RelB, which directs histone H3K9 dimethylation, disrupts assembly of transcription activator NF-κB p65, and induces a sustained switch from the euchromatin to heterochromatin. Here, we report the novel findings that intracellular high mobility group box 1 protein (HMGB1) and nucleosome linker histone H1 protein are necessary components of endotoxin-mediated silencing of TNF-α in THP-1 human promonocytes. HMGB1 binds the TNF-α promoter during transcription silencing and promotes assembly of the repressor RelB. Depletion of HMGB1 by small interfering RNA results in dissociation of RelB from the promoter and partially restores TNF-α transcription. Histone H1, which typically displaces HMGB1 from nucleosomal DNA, also binds concomitantly with HMGB1 to the heterochromatin of the silenced TNF-α promoter. Combined knockdown of HMGB1 and H1 restores binding of the transcriptionally active NF-κB p65 and reestablishes TNF-α mRNA levels. Chromatin reimmunoprecipitation experiments demonstrate that HMGB1 and H1 are likely recruited to TNF-α sequences independently and that their binding correlates with histone H3K9 dimethylation, as inhibition of histone methylation blocks HMGB1 and H1 binding. Moreover, HMGB1- and H1-mediated chromatin modifications are gene specific during endotoxin silencing in that they also bind and repress acute proinflammatory IL-1β, while no binding nor repression of antiinflammatory IκBα is observed. Finally, we find that H1 and HMGB1 bind to the TNF-α a promoter in human leukocytes obtained from patients with SSI. We conclude proinflammatory HMGB1 and structural nucleosome linker H1 couple as a component of the epigenetic complex that silences acute proinflammatory TNF-α during the assembly of heterochromatin in the SSI phenotype.

scholarly journals Glutamylation of Nap1 modulates histone H1 dynamics and chromosome condensation in Xenopus

2015 ◽  
Vol 209 (2) ◽  
pp. 211-220 ◽  
Author(s):  
Kelly E. Miller ◽  
Rebecca Heald
Keyword(s):  
Posttranslational Modification ◽  
Histone H1 ◽  
Chromosome Condensation ◽  
Linker Histone ◽  
Nucleosome Assembly ◽  
Mitotic Chromosomes ◽  
Chromosome Architecture ◽  
Linker Histone H1 ◽  
Egg Extracts ◽  
Sperm Nuclei

Linker histone H1 is required for mitotic chromosome architecture in Xenopus laevis egg extracts and, unlike core histones, exhibits rapid turnover on chromatin. Mechanisms regulating the recruitment, deposition, and dynamics of linker histones in mitosis are largely unknown. We found that the cytoplasmic histone chaperone nucleosome assembly protein 1 (Nap1) associates with the embryonic isoform of linker histone H1 (H1M) in egg extracts. Immunodepletion of Nap1 decreased H1M binding to mitotic chromosomes by nearly 50%, reduced H1M dynamics as measured by fluorescence recovery after photobleaching and caused chromosome decondensation similar to the effects of H1M depletion. Defects in H1M dynamics and chromosome condensation were rescued by adding back wild-type Nap1 but not a mutant lacking sites subject to posttranslational modification by glutamylation. Nap1 glutamylation increased the deposition of H1M on sperm nuclei and chromatin-coated beads, indicating that charge-shifting posttranslational modification of Nap1 contributes to H1M dynamics that are essential for higher order chromosome architecture.

scholarly journals Site-specific ubiquitylation acts as a regulator of linker histone H1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eva Höllmüller ◽  
Simon Geigges ◽  
Marie L. Niedermeier ◽  
Kai-Michael Kammer ◽  
Simon M. Kienle ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Histone H1 ◽  
Linker Histone ◽  
Active Chromatin ◽  
Site Specific ◽  
Linker Histone H1 ◽  
Fundamental Process ◽  
Core Histones ◽  
Wide Scale

AbstractDecoding 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.

scholarly journals The histone variant H2A.W and linker histone H1 co-regulate heterochromatin accessibility and DNA methylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pierre Bourguet ◽  
Colette L. Picard ◽  
Ramesh Yelagandula ◽  
Thierry Pélissier ◽  
Zdravko J. Lorković ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone H1 ◽  
Epigenetic Modifications ◽  
Flowering Plants ◽  
Linker Histone ◽  
Histone Variant ◽  
Null Mutant ◽  
Chromatin Compaction ◽  
Linker Histone H1

AbstractIn 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.

scholarly journals Label-Free Mass Spectrometry-Based Quantification of Linker Histone H1 Variants in Clinical Samples

2020 ◽  
Vol 21 (19) ◽  
pp. 7330
Author(s):  
Roberta Noberini ◽  
Cristina Morales Torres ◽  
Evelyn Oliva Savoia ◽  
Stefania Brandini ◽  
Maria Giovanna Jodice ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Histone H1 ◽  
Histone Variants ◽  
Linker Histone ◽  
Clinical Samples ◽  
Label Free ◽  
Complex Samples ◽  
Linker Histone H1 ◽  
Ideal Tool ◽  
Free Quantification

Epigenetic aberrations have been recognized as important contributors to cancer onset and development, and increasing evidence suggests that linker histone H1 variants may serve as biomarkers useful for patient stratification, as well as play an important role as drivers in cancer. Although traditionally histone H1 levels have been studied using antibody-based methods and RNA expression, these approaches suffer from limitations. Mass spectrometry (MS)-based proteomics represents the ideal tool to accurately quantify relative changes in protein abundance within complex samples. In this study, we used a label-free quantification approach to simultaneously analyze all somatic histone H1 variants in clinical samples and verified its applicability to laser micro-dissected tissue areas containing as low as 1000 cells. We then applied it to breast cancer patient samples, identifying differences in linker histone variants patters in primary triple-negative breast tumors with and without relapse after chemotherapy. This study highlights how label-free quantitation by MS is a valuable option to accurately quantitate histone H1 levels in different types of clinical samples, including very low-abundance patient tissues.

Quantitative Assessment of Transition Proteins 1, 2 Spermatid-Specific Linker Histone H1-Like Protein Transcripts in Spermatozoa from Normozoospermic and Asthenozoospermic Men

2007 ◽  
Vol 53 (4) ◽  
pp. 199-205 ◽  
Author(s):  
Piotr Jedrzejczak ◽  
Bartosz Kempisty ◽  
Artur Bryja ◽  
M. Mostowska ◽  
Magdalena Depa-Martynow ◽  
...  
Keyword(s):  
Quantitative Assessment ◽  
Histone H1 ◽  
Linker Histone ◽  
Linker Histone H1
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