High-Resolution Mapping of H1 Linker Histone Variants in Embryonic Stem Cells

Cao, Kaixiang; Lailler, Nathalie; Zhang, Yunzhe; Kumar, Ashwath; Uppal, Karan; Liu, Zheng; Lee, Eva K.; Wu, Hongwei; Medrzycki, Magdalena; Pan, Chenyi; Ho, Po Y.; Cooper, Guy P.; Dong, Xiao; Bock, Christoph; Bouhassira, Eric E.; Fan, Yuhong

doi:10.1371/journal.pgen.1003417

Cited by 120 publications

(174 citation statements)

References 86 publications

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“…The relative abundance of the main H1 variants was higher on heterochromatic compared with euchromatic transposons (Fig. 5B), resembling the preferences reported for mammalian somatic H1s (Cao et al, 2013;Izzo et al, 2013). In contrast, the abundance of low light-induced H1.3 appeared similar on the two transposon types (Fig.…”

Section: Mapping the Genome-wide Distribution Of H1 Variants Reveals supporting

confidence: 78%

A specialized histone H1 variant is required for adaptive responses to complex abiotic stress and related DNA methylation in Arabidopsis

et al. 2015

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(A.J.).Linker (H1) histones play critical roles in chromatin compaction in higher eukaryotes. They are also the most variable of the histones, with numerous nonallelic variants cooccurring in the same cell. Plants contain a distinct subclass of minor H1 variants that are induced by drought and abscisic acid and have been implicated in mediating adaptive responses to stress. However, how these variants facilitate adaptation remains poorly understood. Here, we show that the single Arabidopsis (Arabidopsis thaliana) stressinducible variant H1.3 occurs in plants in two separate and most likely autonomous pools: a constitutive guard cell-specific pool and a facultative environmentally controlled pool localized in other tissues. Physiological and transcriptomic analyses of h1.3 null mutants demonstrate that H1.3 is required for both proper stomatal functioning under normal growth conditions and adaptive developmental responses to combined light and water deficiency. Using fluorescence recovery after photobleaching analysis, we show that H1.3 has superfast chromatin dynamics, and in contrast to the main Arabidopsis H1 variants H1.1 and H1.2, it has no stable bound fraction. The results of global occupancy studies demonstrate that, while H1.3 has the same overall binding properties as the main H1 variants, including predominant heterochromatin localization, it differs from them in its preferences for chromatin regions with epigenetic signatures of active and repressed transcription. We also show that H1.3 is required for a substantial part of DNA methylation associated with environmental stress, suggesting that the likely mechanism underlying H1.3 function may be the facilitation of chromatin accessibility by direct competition with the main H1 variants.Linker (H1) histones are conserved and ubiquitous structural components of eukaryotic chromatin required for the stabilization of higher order chromatin structure and are generally thought to restrict DNA accessibility. Interestingly, despite their architectural role, H1 histones were shown to be highly mobile and continuously exchanging among chromatin-binding sites (Raghuram et al., 2009). They are also the most variable of the histones, with numerous nonallelic variants coexisting in the same cell. In vertebrates, several evolutionarily conserved subfamilies of H1 can be distinguished (Talbert et al., 2012) and appear to play both redundant and specific roles during development and cellular differentiation (McBryant et al., 2010). There is accumulating evidence that, in animals, regulation of the proportions of H1 variants with different dynamic behavior in chromatin is involved in controlling the accessibility of DNA to trans-acting factors (Jullien et al., 2010;Shahhoseini et al., 2010;Zhang et al., 2012a;Pérez-Montero et al., 2013;Christophorou et al., 2014).Epigenetic mechanisms, including DNA and histone modifications and active nucleosome remodeling, are major players in translating signals about environmental perturbations into adaptive responses at the transc...

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Section: Mapping the Genome-wide Distribution Of H1 Variants Reveals supporting

confidence: 78%

A specialized histone H1 variant is required for adaptive responses to complex abiotic stress and related DNA methylation in Arabidopsis

et al. 2015

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“…4), H1 has been proposed to repress transcription by limiting nucleosome unwrapping as opposed to physically blocking transcription factor binding (76). This is consistent with genome-wide analyses that point to extensive H1 displacement in transcriptionally active genes (68,77). Such a displacement may be aided by chaperones (78).…”

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confidence: 58%

Yeast HMO1: Linker Histone Reinvented

Panday

Grove

2017

Microbiol Mol Biol Rev

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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.

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“…Binding of H1.2 has been associated with the repressive histone marks H3K9 trimethylation (H3K9me3) and H3K27me3 in certain contexts (40,48,49). Therefore, ChIP for H3K9me3 and H3K27me3 at the CISH promoter was performed upon HMGN2 knockdown.…”

Section: Prl Treatment Induces Chromatin Decompaction and Promotes Bimentioning

confidence: 99%

Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells

Schauwecker

Kim

Licht

et al. 2017

Journal of Biological Chemistry

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Edited by John M. DenuThe hormone prolactin (PRL) contributes to breast cancer pathogenesis through various signaling pathways, one of the most notable being the JAK2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL-induced activation of the transcription factor STAT5 results in the up-regulation of numerous genes implicated in breast cancer pathogenesis. However, the molecular mechanisms that enable STAT5 to access the promoters of these genes are not well understood. Here, we show that PRL signaling induces chromatin decompaction at promoter DNA, corresponding with STAT5 binding. The chromatin-modifying protein high mobility group nucleosomal binding domain 2 (HMGN2) specifically promotes STAT5 accessibility at promoter DNA by facilitating the dissociation of the linker histone H1 in response to PRL. Knockdown of H1 rescues the decrease in PRL-induced transcription following HMGN2 knockdown, and it does so by allowing increased STAT5 recruitment. Moreover, H1 and STAT5 are shown to function antagonistically in regulating PRL-induced transcription as well as breast cancer cell biology. While reduced STAT5 activation results in decreased PRL-induced transcription and cell proliferation, knockdown of H1 rescues both of these effects. Taken together, we elucidate a novel mechanism whereby the linker histone H1 prevents STAT5 binding at promoter DNA, and the PRL-induced dissociation of H1 mediated by HMGN2 is necessary to allow full STAT5 recruitment and promote the biological effects of PRL signaling.In the mammary gland, signals from the polypeptide hormone prolactin (PRL) are essential for normal development (1-4), and these physiological effects are mediated through the homologous transcription factors signal transducer and activator of transcription 5a and 5b (referred to as STAT5) (5). PRL signals by binding to the PRL receptor (PRLR), 2 a transmembrane receptor of the cytokine receptor superfamily. Binding of PRL to the PRLR results in the activation of STAT5 via phosphorylation by the tyrosine kinase Janus kinase 2 (JAK2) (6 -8). Phosphorylated STAT5 dimerizes, and the active STAT5 dimers translocate to the nucleus. In the nucleus, STAT5 recognizes and binds to consensus elements in the DNA, which induces the expression of STAT5 target genes (9).PRL-induced STAT5 activation results in the up-regulation of many pro-proliferative genes (10 -12). Although essential for proper mammary gland development, aberrant PRL signaling and STAT5 activation also contribute to breast cancer pathogenesis. Transgenic mice that overexpress PRL in the mammary epithelium develop mammary tumors, which can be either estrogen receptor-positive or -negative (13). In epidemiologic studies, women with elevated serum PRL are at an increased risk of developing breast cancer (14 -17). PRL also enhances the proliferation, motility, and survival of breast cancer cells (18 -20). Similarly, overexpression of STAT5 in the mammary gland of transgenic mice results in mammary tumor development (21), whereas hemizygous los...

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High-Resolution Mapping of H1 Linker Histone Variants in Embryonic Stem Cells

Cited by 120 publications

References 86 publications

A specialized histone H1 variant is required for adaptive responses to complex abiotic stress and related DNA methylation in Arabidopsis

A specialized histone H1 variant is required for adaptive responses to complex abiotic stress and related DNA methylation in Arabidopsis

Yeast HMO1: Linker Histone Reinvented

Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells

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