Effects of H1 Histone Variant Overexpression on Chromatin Structure

Gunjan, Akash; Alexander, Barbara T.; Sittman, Donald B.; Brown, David T.

doi:10.1074/jbc.274.53.37950

Cited by 70 publications

(48 citation statements)

References 43 publications

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“…Correlations between H1 content and NRL have been observed in other systems: nuclei from ox cerebral cortex neurons have a short NRL (162 bp) compared with glial nuclei (201 bp) and a corresponding change in H1 content from 0.45 molecule to 1.04 molecules per nucleosome (35). Overexpression of H1 0 in cultured mouse fibroblasts resulted in a 15-bp increase in NRL (20), and Tetrahymena lacking macronuclear H1 has an NRL that is ϳ10 bp shorter than that of the wild type (M. A. Gorovsky, personal communication). Inclusion of linker histones in in vitro reconstitution systems results in increased NRLs (5) and can also restore the native spacing of randomized nucleosomal arrays (43).…”

Section: Discussionmentioning

confidence: 75%

H1 Linker Histones Are Essential for Mouse Development and Affect Nucleosome Spacing In Vivo

Fan

Nikitina

Morin‐Kensicki

et al. 2003

Molecular and Cellular Biology

292

355

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Most eukaryotic cells contain nearly equimolar amounts of nucleosomes and H1 linker histones. Despite their abundance and the potential functional specialization of H1 subtypes in multicellular organisms, gene inactivation studies have failed to reveal essential functions for linker histones in vivo. Moreover, in vitro studies suggest that H1 subtypes may not be absolutely required for assembly of chromosomes or nuclei. By sequentially inactivating the genes for three mouse H1 subtypes (H1c, H1d, and H1e), we showed that linker histones are essential for mammalian development. Embryos lacking the three H1 subtypes die by midgestation with a broad range of defects. Triple-H1-null embryos have about 50% of the normal ratio of H1 to nucleosomes. Mice null for five of these six H1 alleles are viable but are underrepresented in litters and are much smaller than their littermates. Marked reductions in H1 content were found in certain tissues of these mice and in another compound H1 mutant. These results demonstrate that the total amount of H1 is crucial for proper embryonic development. Extensive reduction of H1 in certain tissues did not lead to changes in nuclear size, but it did result in global shortening of the spacing between nucleosomes.DNA in the eukaryotic nucleus is organized into a highly compact nucleoprotein complex referred to as chromatin (48,53). The histones constitute a family of proteins that are intimately involved in organizing chromatin structure. The nucleosome core particle, the highly conserved unit of chromatin organization in all eukaryotes, consists of an octamer of four core histones (H2A, H2B, H3, and H4) around which about 145 bp of DNA is wrapped. The chromatin fiber also contains a fifth histone, the linker histone (usually referred to as H1), which can bind to core particles and protect an additional ϳ20 bp of DNA (linker DNA) from nuclease digestion. The precise location and stoichiometry of H1 within the chromatin fiber are uncertain (45,46,49), but in higher eukaryotes, there is, on average, nearly one H1 molecule for each core particle (48). Most of our knowledge about the role of H1 in chromatin structure is based on in vitro experiments. These studies indicate that two principal functions of linker histones are to organize and stabilize the DNA as it enters and exits the core particle and to facilitate the folding of nucleosome arrays into more compact structures (19,38). Despite the presumed fundamental role of linker histones in chromatin structure, elimination of H1 in Tetrahymena, Saccharomyces cerevisiae, and Aspergillus nidulans and silencing of H1 in Ascobolus immersus showed that H1 is not essential in these unicellular eukaryotes (3,34,39,41,47).In higher organisms, additional levels of control on chromatin organization and function are available because of the existence of multiple nonallelic linker histone variants or subtypes (6, 33). In mice, there are at least eight H1 subtypes, including the widely expressed subtypes H1a through H1e, the testis-specific subtype H1...

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Section: Discussionmentioning

confidence: 75%

H1 Linker Histones Are Essential for Mouse Development and Affect Nucleosome Spacing In Vivo

Fan

Nikitina

Morin‐Kensicki

et al. 2003

Molecular and Cellular Biology

292

355

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“…The observations of Nagaraja et al (40) demonstrated that trout liver histone H1b (equivalent of mammalian histone H1°) was more effective than H1a in producing higher-order chromatin structures. A positive correlation was found between the relative amount of H1°and chromatin condensation (81), and overexpression of histone H1°in terminally differentiated cells was shown to induce chromatin condensation (39). In contrast, histone H1°was found to induce structures that were more relaxed and less protected against nuclease attack than those obtained with other H1 subtypes (36,81).…”

Section: Discussionmentioning

confidence: 80%

Histone H1 and chromatin interactions in human fibroblast nuclei after H1 depletion and reconstitution with H1 subfractions

et al. 2004

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Background:Linker histones constitute a family of lysinerich proteins associated with nucleosome core particles and linker DNA in eukaryotic chromatin. In permeabilized cells, they can be extracted from nuclei by using salt concentration in the range of 0.3 to 0.7 M. Although other nuclear proteins are also extracted at 0.7 M salt, the remaining nucleus represents a template that is relatively intact. Methods: A cytochemical method was used to study the affinity of reconstituted linker histones for chromatin in situ in cultured human fibroblasts. We also investigated their ability to condense chromatin by using DNA-specific osmium ammine staining for electron microscopy. Results: Permeabilized and H1-depleted fibroblast nuclei were suitable for the study of linker histone-chromatin

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“…Several previous studies have proposed that H1 0 , the closest mammalian homologue of avian histone H5, plays a major role in chromatin condensation in cultured cells (56,57) and in terminally differentiated cells that undergo global heterochromatization (58,59). In contrast to H1 0 , H1c has been implicated in organizing more open chromatin structures (57,60).…”

Section: Discussionmentioning

confidence: 99%

Developmentally Regulated Linker Histone H1c Promotes Heterochromatin Condensation and Mediates Structural Integrity of Rod Photoreceptors in Mouse Retina

Popova

Grigoryev

Fan

et al. 2013

Journal of Biological Chemistry

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Background: Heterochromatin condenses in the middle of rod cell nuclei during retina maturation. Results: The level of linker histone H1c increases during retina maturation. Rod photoreceptors in triple H1 knock-out mice have less compact chromatin. Conclusion: H1c is a key architectural factor for chromatin condensation in the rod photoreceptor. Significance: Histone H1c expression may be genetically modified to promote rod photoreceptor maturation and retina integrity.Mature rod photoreceptor cells contain very small nuclei with tightly condensed heterochromatin. We observed that during mouse rod maturation, the nucleosomal repeat length increases from 190 bp at postnatal day 1 to 206 bp in the adult retina. At the same time, the total level of linker histone H1 increased reaching the ratio of 1.3 molecules of total H1 per nucleosome, mostly via a dramatic increase in H1c. Genetic elimination of the histone H1c gene is functionally compensated by other histone variants. However, retinas in H1c/H1e/H1 0 triple knock-outs have photoreceptors with bigger nuclei, decreased heterochromatin area, and notable morphological changes suggesting that the process of chromatin condensation and rod cell structural integrity are partly impaired. In triple knock-outs, nuclear chromatin exposed several epigenetic histone modification marks masked in the wild type chromatin. Dramatic changes in exposure of a repressive chromatin mark, H3K9me2, indicate that during development linker histone plays a role in establishing the facultative heterochromatin territory and architecture in the nucleus. During retina development, the H1c gene and its promoter acquired epigenetic patterns typical of rod-specific genes. Our data suggest that histone H1c gene expression is developmentally up-regulated to promote facultative heterochromatin in mature rod photoreceptors.During mammalian development, cells committed to differentiate into a specific tissue withdraw from the cell cycle and start a process of tissue maturation that involves up-regulation of genes specific for the differentiated tissue and down-regulation of genes specific for progenitor cells (1, 2). This developmentally regulated process culminates in formation of compact blocks of heterochromatin inside the nuclei and spatial segregation of heterochromatin and euchromatin domains (3). Chromatin condensation prevents certain transcription factors from activating genes in the compact chromatin (4). Recent studies suggest that each tissue type has its own unique program that orchestrates tissue maturation, with specific sets of chromatin architectural and remodeling proteins, histone modifications, and micro-RNA (5-12).The mammalian retina is a part of the CNS and is derived from the optic cup, an outgrowth of forebrain neuroepithelium formed early in CNS development. Six major neuronal and one glial cell types are generated from the multipotential retinal progenitors in a stereotypic temporal sequence. In mice the terminal differentiation of retinal cells spans from embryonic day ...

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Effects of H1 Histone Variant Overexpression on Chromatin Structure

Cited by 70 publications

References 43 publications

H1 Linker Histones Are Essential for Mouse Development and Affect Nucleosome Spacing In Vivo

H1 Linker Histones Are Essential for Mouse Development and Affect Nucleosome Spacing In Vivo

Histone H1 and chromatin interactions in human fibroblast nuclei after H1 depletion and reconstitution with H1 subfractions

Developmentally Regulated Linker Histone H1c Promotes Heterochromatin Condensation and Mediates Structural Integrity of Rod Photoreceptors in Mouse Retina

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