Histone H1 Is Dispensable for Methylation-Associated Gene Silencing in <i>Ascobolus immersus</i>and Essential for Long Life Span

Barra, José L.; Rhounim, L; Rossignol, Jean‐Luc; Faugeron, Godeleine

doi:10.1128/mcb.20.1.61-69.2000

Cited by 90 publications

(77 citation statements)

References 64 publications

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“…However, there have been an increasing number of examples in which H1 plays a more specific role in transcription by differentially acting at the level of individual genes. The original model for this H1 specificity is based on the results obtained from gene knock-out experiments in Tetrahymena, fungus, and yeast (15,52,53). These studies showed that deletion of H1 gene keeps the organism alive, but specific subsets of genes are differentially regulated.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of a Novel H1.2 Complex That Acts as a Repressor of p53-mediated Transcription

Kim

Choi

Heo

et al. 2008

Journal of Biological Chemistry

110

109

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Linker histone H1 has been generally viewed as a global repressor of transcription by preventing the access of transcription factors to sites in chromatin. However, recent studies suggest that H1 can interact with other regulatory factors for its action as a negative modulator of specific genes. To investigate these aspects, we established a human cell line expressing H1.2, one of the H1 subtypes, for the purification of H1-interacting proteins. Our results showed that H1.2 can stably associate with sets of cofactors and ribosomal proteins that can significantly repress p53-dependent, p300-mediated chromatin transcription. This repressive action of H1.2 complex involves direct interaction of H1.2 with p53, which in turn blocks p300-mediated acetylation of chromatin. YB1 and PUR␣, two factors present in the H1.2 complex, together with H1.2 can closely recapitulate the repressive action of the entire H1.2 complex in transcription. Chromatin immunoprecipitation and RNA interference analyses further confirmed that the recruitment of YB1, PUR␣, and H1.2 to the p53 target gene Bax is required for repression of p53-induced transcription. Therefore, these results reveal a previously unrecognized function of H1 as a transcriptional repressor as well as the underlying mechanism involving specific sets of factors in this repression process.Histones are the major protein components to compact genomic DNA into the limited volume of the nucleus as a highly organized chromatin structure. The basic element of chromatin is the nucleosome, which consists of 146 base pairs of DNA wrapped around an octameric core of histones containing two molecules each of H2A, H2B, H3, and H4 (1-4). This repeating unit of chromatin is associated with another type of histone called linker histone H1 to achieve an additional level of compaction, making genes inaccessible to transcription factors and preventing their expression (5-9). Mammalian cells have at least eight histone H1 subtypes including H1.1 through H1.5 and somatic cell-specific H1o as well as germ cell-specific H1t and H1oo, all consisting of a highly conserved globular domain and less conserved N-and C-terminal domains (6,8,10). The existence of multiple H1 subtypes and the diversity of their amino acid sequences raise the possibility that individual subtypes have nonredundant functions in various cellular processes. In addition, the expression of each H1 subtype depends on the tissue, phase of the cell cycle, and developmental stage, further suggesting the specific contribution of linker histone subtypes for regulation of various cellular processes (6,8,11).Although most studies have focused on the contribution of H1 as a structural component of the nucleosome, it is becoming apparent that H1 also acts as a repressor for specific gene transcription (12)(13)(14)(15). This repressive capacity of H1 on transcription appears to be accomplished by its localization at particular chromosomal domains with specific transcription regulators. Msx1 recruits a linker histone H1 to the MyoD gene,...

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Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of a Novel H1.2 Complex That Acts as a Repressor of p53-mediated Transcription

Kim

Choi

Heo

et al. 2008

Journal of Biological Chemistry

110

109

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“…These observations demonstrate that a nucleosomal architecture containing methylated DNA (22,23,77). In Ascobolus immersus elimination for some transcription factors, acetylation of the amino-terminal tails substantially weakens the conof histone H1 is without effect on methylation-dependent gene silencing (8). Moreover, recent in vivo straints on DNA imposed by the core histones.…”

Section: El-osta and Wolffementioning

confidence: 99%

DNA Methylation and Histone Deacetylation in the Control of Gene Expression: Basic Biochemistry to Human Development and Disease

2001

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DNA methylation is a major determinant in the epigenetic silencing of genes. The mechanisms underlying the targeting of DNA methylation and the subsequent repression of transcription are relevant to human development and disease, as well as for attempts at somatic gene therapy. The success of transgenic technologies in plants and animals is also compromised by DNA methylation-dependent silencing pathways. Recent biochemical experiments provide a mechanistic foundation for understanding the influence of DNA methylation on transcription. The DNA methyltransferase Dnmt1, and several methyl-CpG binding proteins, MeCP2, MBD2, and MBD3, all associate with histone deacetylase. These observations firmly connect DNA methylation with chromatin modifications. They also provide new pathways for the potential targeting of DNA methylation to repressive chromatin as well as the assembly of repressive chromatin on methylated DNA. Here we discuss the implications of the methylation-acetylation connection for human cancers and the developmental syndromes Fragile X and Rett, which involve a mistargeting of DNA methylation-dependent repression.

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“…One proposal is that H1 hyperphosphorylation itself might serve as a mitotic "trigger" and not the actual physical means for condensation (Roth and Allis, 1992 These data point towards the fact that specific H1 subtypes and their phosphorylation states may have specific functional roles in chromatin remodeling events which are responsible for transcriptional regulation that takes place during various biological processes such as development, differentiation, DNA repair (Downs et al, 2003), apoptosis (Konishi et al, 2003;Okamura et al, 2007) and lifespan (Barra et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

H1 histone subtype constitution and phosphorylation state of the ageing cell system of human peripheral blood lymphocytes

Happel

Doenecke

Sekeri‐Pataryas

et al. 2008

Experimental Gerontology

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Histone H1 Is Dispensable for Methylation-Associated Gene Silencing in Ascobolus immersusand Essential for Long Life Span

Cited by 90 publications

References 64 publications

Isolation and Characterization of a Novel H1.2 Complex That Acts as a Repressor of p53-mediated Transcription

Isolation and Characterization of a Novel H1.2 Complex That Acts as a Repressor of p53-mediated Transcription

DNA Methylation and Histone Deacetylation in the Control of Gene Expression: Basic Biochemistry to Human Development and Disease

H1 histone subtype constitution and phosphorylation state of the ageing cell system of human peripheral blood lymphocytes

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