Mice develop normally without the H1(0) linker histone.

Sirotkin, Allen; Edelmann, Winfried; Cheng, Genhong; Klein‐Szanto, Andres J.; Kucherlapati, Raju; Skoultchi, Arthur I.

doi:10.1073/pnas.92.14.6434

Cited by 174 publications

(149 citation statements)

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“…Expression of the chimeric H1 also led to recruitment of DNMT1 and DNMT3B to the H19 and Gtl2 ICRs, whereas expression of H1c and a truncated H1d lacking this region of the CTD did not lead to recruitment of the two DNMTs. Gene inactivation studies in mice have not revealed essential functions for any of these histone H1 subtypes, including H1c and H1(0) (15)(16)(17). Interestingly however, we reported previously that the genes encoding H1(0) and H1c exhibit differences in their regulation compared with the genes encoding the four other subtypes (40)(41)(42).…”

Section: Discussionmentioning

confidence: 93%

“…Mammals contain at least eight histone H1 subtypes or variants that differ in amino acid sequences and expression during development (12)(13)(14). Functional differences among these subtypes have been difficult to identify because they appear to act redundantly in development (14)(15)(16)(17). Although the precise location of histone H1 within the chromatin fiber is uncertain, it is known that histone H1 resides outside the nucleosome core particle, where it associates with the DNA as it enters and exits the core particle and protects an additional ∼20 bp of DNA (linker DNA).…”

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confidence: 99%

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H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation

Yang

Kim

Toro

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

105

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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.mouse embryonic stem cell | H1 histone triple knockout T wo major types of epigenetic marks occur in mammalian genomes, DNA methylation and posttranslational modifications of histones (1, 2). The methylation of cytosines in mammalian DNA occurs primarily at CpG dinucleotides and is essential for normal mammalian development (1, 3). Perturbations of DNA methylation patterns are thought to play a role in cancer development (4). There are two classes of mammalian DNA methyltransferases (DNMTs), one that functions primarily to establish DNA methylation de novo (DNMT3A and DNMT3B) and the other to maintain it (DNMT1) (3). DNA methylation can have profound effects on gene expression and is most often associated with transcriptional silencing (1, 2). Accumulating evidence indicates the existence of crosstalk between the DNA methylation and core histone modification systems (1, 2). For example, mouse ES cells deficient for the histone H3 lysine 9 (H3K9) methyltransferases Suv39h1/h2 exhibit hypomethylation of CpGs at a subset of repetitive DNA elements (5). Additionally, several lines of evidence indicate that the presence of unmethylated lysine 4 of histone H3 (H3K4) in chromatin favors de novo methylation of DNA (6-9). Despite these advances, the factors in chromatin that coordinate DNA methylation and histone H3 methylation have not been identified.In this study, we investigated the role of the linker histone H1 in regulating DNA methylation and histone H3 methylation at the H19 and Gtl2 loci in mouse ES cells. H1 is the most distinct of the five histone proteins (H1, H2A, H2B, H3, and H4) in chromatin (10,11). Mammals contain at least eight histone H1 subtypes or variants that differ in amino acid sequences and expression during development (12-14). Functional differences among these subtypes have been difficult to identif...

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation

Yang

Kim

Toro

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

105

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“…Nuclei and chromatin preparation, and extraction of basic NPs (BNPs) from total testes or sonication-resistant spermatids (SRS) were performed as described (20,21,27).…”

Section: Methodsmentioning

confidence: 99%

HILS1 is a spermatid-specific linker histone H1-like protein implicated in chromatin remodeling during mammalian spermiogenesis

Yan

Burns

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

165

136

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Chromatin remodeling is a major event that occurs during mammalian spermiogenesis, the process of spermatid maturation into spermatozoa. Nuclear condensation during spermiogenesis is accomplished by replacing somatic histones (linker histone H1 and core histones) and the testis-specific linker histone, H1t, with transition proteins and protamines. It has long been thought that H1t is the only testis-specific linker histone, and that all linker histones are replaced by transition proteins, and subsequently by protamines during spermiogenesis. Here, we report the identification and characterization of a spermatid-specific linker histone H1-like protein (termed HILS1) in the mouse and human. Both mouse and human HILS1 genes are located in intron 8 of the ␣-sarcoglycan genes. HILS1 is highly expressed in nuclei of elongating and elongated spermatids (steps 9 -15). HILS1 displays several biochemical properties that are similar to those of linker histones, including the abilities to bind reconstituted mononucleosomes, produce a chromatosome stop during micrococcal nuclease digestion, and aggregate chromatin. Because HILS1 is expressed in late spermatids that do not contain core histones, HILS1 may participate in spermatid nuclear condensation through a mechanism distinct from that of linker histones. Because HILS1 also belongs to the large winged helix͞forkhead protein superfamily, HILS1 may also regulate gene transcription, DNA repair, and͞or other chromosome processes during mammalian spermiogenesis.spermatogenesis ͉ transition nuclear proteins ͉ in silico subtraction ͉ genome database mining H istones are a family of basic proteins that organize eukaryotic DNA into a compact chromatin. There are five major classes of histones, the core histones H2A, H2B, H3, and H4, and the linker histones, H1. Two of each of the four core histones constitute an octamer unit of the nucleosome particle. H1 histones bind to DNA in the nucleosome and to the linker DNA between nucleosomes, thereby facilitating the compaction of nucleosomes into a 30-nm chromatin fiber and higher-order chromatin structures (1). These interactions between histones and DNA modulate gene activity, and both core and H1 histones have profound effects on transcription (2, 3). Among the five histone classes, H1 histones exhibit the most diversity. In mice and humans, there are eight previously described H1 subtypes, including the five somatic subtypes H1a-H1e, the replacement subtype H1o, the testis-specific linker-histone H1t (4-6), and the oocyte-specific H1 linker histone, H1foo (7). The genomic organizations of these histone H1 genes are conserved (8,9).Spermatogenesis is the process of development of male germ cells from spermatogonia to highly differentiated spermatozoa. During spermatogenesis, chromatin is restructured, and dramatic changes in histone gene expression are observed (10). In spermatogonia and preleptotene spermatocytes (cells undergoing DNA replication), the H1a and H1b linker histones are expressed (11). During meiotic prophase, striking ...

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“…For instance, in a Saccharomyces cerevisiae mutant lacking one of two H2A/ H2B gene pairs, the expression of the residual pair increases to compensate for the deficiency (Osley & Hereford 1981;Moran et al 1990). In mice devoid of H1 0 , other H1 genes are transcribed more than in the wild-type mice (Sirotkin et al 1995). In three types of chicken DT40 mutants (the above-mentioned 01H1-and H2B-V-deficient mutants, and the H3-IV/H3-Vdeficient mutant), expression of the remaining five H1 genes, seven H2B genes and nine H3 genes increases to compensate for the mutations (Seguchi et al 1995;Takami et al 1995a,b).…”

Section: Introductionmentioning

confidence: 99%

A single copy of linker H1 genes is enough for proliferation of the DT40 chicken B cell line, and linker H1 variants participate in regulation of gene expression

Yasuda

Nakayama

1997

Genes to Cells

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Background: There is general agreement that large numbers of histone H1 are necessary for maintenance of the higher order structure of chromatin in higher eukaryotes. The chicken H1 gene family comprises six members per haploid genome, the total copy number being 12, and they encode six H1 variants which are considerably different from each other in amino acid sequence. We recently established that in two chicken DT40 mutants (1/ 2D110kb and D57kb), which lack, respectively, one allele of the gene cluster of 110 kb carrying six H1 genes, plus 33 core histone genes, and two copies each of four of the six H1 genes included in an Ϸ 57 kb segment of the cluster, expression of the remaining H1 genes is increased, resulting in constant steady-state levels of total H1 mRNAs. These results gave rise to the simple questions of how many H1 genes and how many H1 variants, at minimum, are necessary for the viability of DT40 cells.

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Mice develop normally without the H1(0) linker histone.

Abstract: Hi histones bind to the linker DNA between nucleosome core particles and facilitate the folding of chromatin into a 30-nm fiber. Mice contain at least seven nonal-

Cited by 174 publications

References 42 publications

H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation

H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation

HILS1 is a spermatid-specific linker histone H1-like protein implicated in chromatin remodeling during mammalian spermiogenesis

A single copy of linker H1 genes is enough for proliferation of the DT40 chicken B cell line, and linker H1 variants participate in regulation of gene expression

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