Structure and expression of the human gene encoding testicular H1 histone (H1t)

Drabent, Birgit; Kardalinou, E; Doenecke, Detlef

doi:10.1016/0378-1119(91)90284-i

Cited by 81 publications

(59 citation statements)

References 33 publications

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“…Although the H1t histone consists of a three-domain structure like other H1s, the mouse H1t amino acid sequence shares only 50% identity with its closest relative among the mouse H1s. Homologs of H1t have been identified in many mammals (7,10,14,34), and germ cellspecific linker histones have been described for other phyla as well (19,22,36). Germ cell-specific core histone genes and proteins have also been described for H2a, H2b, H3 (15,30,38).…”

Section: Discussionmentioning

confidence: 99%

Normal Spermatogenesis in Mice Lacking the Testis-Specific Linker Histone H1t

Lin

Sirotkin²,

Skoultchi

2000

Molecular and Cellular Biology

129

124

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H1 histones bind to linker DNA and nucleosome core particles and facilitate the folding of chromatin into a more compact structure. Mammals contain seven nonallelic subtypes of H1, including testis-specific subtype H1t, which varies considerably in primary sequence from the other H1 subtypes. H1t is found only in pachytene spermatocytes and early, haploid spermatids, constituting as much as 55% of the linker histone associated with chromatin in these cell types. To investigate the role of H1t in spermatogenesis, we disrupted the H1t gene by homologous recombination in mouse embryonic stem cells. Mice homozygous for the mutation and completely lacking H1t protein in their germ cells were fertile and showed no detectable defect in spermatogenesis. Chromatin from H1t-deficient germ cells had a normal ratio of H1 to nucleosomes, indicating that other H1 subtypes are deposited in chromatin in place of H1t and presumably compensate for most or all H1t functions. The results indicate that despite the unique primary structure and regulated synthesis of H1t, it is not essential for proper development of mature, functional sperm.The histones are a family of basic proteins that are involved in organizing the DNA in the nuclei of eukaryotic cells into a compact structure called chromatin. There are five major classes of histones, the core histones H2A, H2B, H3, and H4 and the linker histone H1. Two molecules of each of the core histones constitute the protein octamer of the nucleosome core particle. H1 histones bind to DNA in the nucleosome core particle and to the linker DNA between nucleosomes. These interactions are thought to facilitate the folding of nucleosomes into the 30-nm chromatin fiber and higher-order chromatin structures (39,42). Interactions between histones and DNA would be expected to modulate gene activity, and recent evidence clearly shows that both the core histones and H1 can have a profound effect on transcription (reviewed in references 18, 43, and 44).Among the five classes of histones, the H1 histones exhibit the most diversity. For mice seven H1 subtypes have been described (24, 25), including the "somatic" subtypes H1a through H1e, the replacement subtype H1 o , and the testisspecific linker histone H1t. These seven H1 subtypes are also present in humans, and the genomic organization of the genes encoding the H1 subtypes in humans appears to be very similar to that in mice (12,40).Within the H1 family of proteins, the testis-specific H1t subtype is unique in that it is the only member exhibiting a truly tissue-specific pattern of expression. Although the other six H1 subtypes display distinct patterns of expression during differentiation and development, they are all expressed in numerous tissues (24-26). On the other hand, the H1t gene is transcribed exclusively in mid-and late-pachytene spermatocytes (10, 13, 16), and H1t protein is found only in pachytene spermatocytes and early, haploid spermatids (11,17,29), in which it constitutes up to 55% of the total H1 linker histone in chromatin (29). M...

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Section: Discussionmentioning

confidence: 99%

Normal Spermatogenesis in Mice Lacking the Testis-Specific Linker Histone H1t

Lin

Sirotkin²,

Skoultchi

2000

Molecular and Cellular Biology

129

124

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“…Further, the ratio of the total amount of linker histones to that of H2b was the same in liver chromatin from the two types of animals ( (36). In contrast to other mammalian HI genes which encode nonpolyadenylylated mRNAs (37)(38)(39), the H10 gene produces polyadenylylated mRNAs (29,40,41). This aspect and differences in transcriptional promoter elements (27,42,43) probably account for the lack of cell cycle regulation of HI0 gene expression compared with the highly regulated expression of other Hi genes during S phase.…”

Section: Generation Of Esmentioning

confidence: 91%

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

Sirotkin

Edelmann

Cheng

et al. 1995

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

175

136

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“…4B). Moreover, a putative site of phosphorylation that is very conserved in all somatic histone H1 s within the C-terminal domain is missing in mammalian Hlt (Drabent et al, 1991).…”

Section: Testis-specific Linker Histones ( H L T )mentioning

confidence: 99%

“…A testis-specific linker histone (Hlt) is expressed in the spermatogenic cells in many mammals (Seyedin et al, 1981 ;Drabent et al, 1991;Koppel et al, 1994). Hlt mRNA accumulates exclusively in pachytene primary spermatocytes (Grimes et al, 1990).…”

Section: Testis-specific Linker Histones ( H L T )mentioning

confidence: 99%

“…The protein persists through meiosis and finally is replaced by transition proteins and protamines during spermatid maturation (Meistrich, 1989). The gene encoding this variant has been cloned from rat (Cole et al, 1986;Grimes et al, 1990), monkey (Koppel et al, 1994) and human (Drabent et al, 1991). The coding sequence has significant differences to the common linker histones.…”

Section: Testis-specific Linker Histones ( H L T )mentioning

confidence: 99%

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Developmentally regulated expression of linker‐histone variants in vertebrates

Khochbin

Wolffe

1994

European Journal of Biochemistry

101

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The identification of histone H1 variants in vertebrates suggests that these proteins may have specialized functions. During embryonic development, a correspondence between the expression of each of the linker-histone variants and the proliferative and transcriptional activity of embryonic cells can be observed. Analysis of the developmentally regulated expression of these variants leads to the subdivision of these variants into distinct classes. This subdivision may also provide insight into the significance of the differential expression of variants and the roles individual linker histones have in chromatin structure and function.Linker histones have long been known to interact with the variable length of linker DNA that lies between nucleosome cores within chromatin (van Holde, 1989). This interaction is believed to facilitate the folding of nucleosomal arrays into higher-order structures. This mundane packaging role is, not, however, the only role linker histones have to play. Studies on the structure of linker histones, their interaction with the nucleosome and their roles in controlling gene activity indicate that this family of proteins has not only an important architectural role, but also an essential regulatory role in transcription. In vertebrates, several different variants of linker histones have been described and the expression of their genes studied. It is useful to examine the properties and expression of these variants, since this analysis leads to a better understanding of the relevance of this diversity for particular cellular activities during development.Linker histones may be subdivided into four major classes according to both the timing of their expression and their cell-type specificity during development. This division, based on the pattern of expression, corresponds also to distinct properties of proteins in each class. In general, a linker histone presents a tripartite structure; an N-terminal tail, a globular domain and a relatively long C-terminal tail. Members of each class have conserved this structural feature but can ble distinguished mainly by the length of the N-terminal and C-terminal tails and the nature of the peptide sequence, i.e. the number of acidic and basic amino acids as well as the nature of the basic residues.Cleavage linker histones are expressed during oogenesis and during early embryogenesis. The normal somatic form of linker histone (Hl) progressively accumulates in nuclei after the initiation of zygotic expression and, thereafter, is Correspondence to S. Khochbin,

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Structure and expression of the human gene encoding testicular H1 histone (H1t)

Cited by 81 publications

References 33 publications

Normal Spermatogenesis in Mice Lacking the Testis-Specific Linker Histone H1t

Normal Spermatogenesis in Mice Lacking the Testis-Specific Linker Histone H1t

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

Developmentally regulated expression of linker‐histone variants in vertebrates

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