The mouse histone H1 genes: gene organization and differential regulation

Wang, Zeng Feng; Sirotkin, Allen; Buchold, Gregory M.; Skoultchi, Arthur I.; Marzluff, William F.

doi:10.1006/jmbi.1997.1166

Cited by 87 publications

(97 citation statements)

References 60 publications

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“…1). H1T2 is encoded by an intronless gene present on chromosome 15 (F2), whereas the other histone H1 genes are on chromosome 13 (22). Database searches identified a putative 234-aa human H1T2 orthologue encoded by chromosome 12 (locus q13.11).…”

Section: Resultsmentioning

confidence: 99%

Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis

Martianov

Brancorsini

Catena

et al. 2005

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

190

168

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Spermiogenesis entails a major biochemical and morphological restructuring of the germ cell involving replacement of the somatic histones by protamines packing the DNA into the condensed spermatid nucleus and elimination of the cytoplasm during the elongation phase. We describe H1T2, an histone H1 variant selectively and transiently expressed in male haploid germ cells during spermiogenesis. In round and elongating spermatids, H1T2 specifically localizes to a chromatin domain at the apical pole, revealing a polarity in the spermatid nucleus. Inactivation by homologous recombination shows that H1T2 is critical for spermiogenesis as male H1t2 ؊/؊ mice have greatly reduced fertility. Analysis of spermiogenesis in H1t2 mutant mice shows delayed nuclear condensation and aberrant elongation. As a result, mutant spermatids are characterized by the presence of residual cytoplasm, acrosome detachment, and fragmented DNA. Hence, H1T2 is a protein required for proper cell restructuring and DNA condensation during the elongation phase of spermiogenesis.chromatin ͉ mouse ͉ protamine ͉ acrosome M ammalian spermatogenesis involves the differentiation of diploid spermatogonia into spermatocytes and then, through two successive meiotic divisions, into haploid round spermatids. During spermiogenesis, the haploid round spermatids undergo an elongation phase, transforming them into mature spermatozoa. This process entails a major biochemical and morphological restructuring of the germ cell where the majority of the somatic histones are replaced, first by transition proteins, then protamines packing the DNA into the sperm cell nucleus.Differentiating male germ cells use specialized transcriptional regulatory mechanisms involving testis-specific paralogues of transcription factors such as TLF͞TRF2, ALF, and TAF7L (1-3). In addition, male germ cells contain specialized chromatin components such as H1T, a histone H1 variant specifically expressed in pachytene spermatocytes and early haploid cells (4), and HILS1, a histone H1-related protein specifically expressed in elongating and elongated spermatids (5). However, no spermatogenesis abnormalities are observed in mice lacking the H1t gene, perhaps because of redundancy with the somatic H1.1, which is also expressed at this stage (6-9). This finding contrasts with the reduced fertility and defective spermiogenesis in mice lacking transition proteins 1 or 2 or haploinsufficient for protamines 1 or 2 (10-12). Thus, whereas H1 histones have been proposed to play a role in the formation of higher-order chromatin structure, the physiological functions of the tissue-specific variants remain obscure. Here, we describe a male germ cellspecific H1-related protein, H1T2, that plays a critical role during the elongation phase of spermiogenesis. Materials and MethodsCloning and Inactivation of H1t2. The H1t2 cDNA was cloned from a mouse testis cDNA library by screening with the short mouse TEST640 EST probe as described (2, 13). 5Ј RACE using mouse testis RNA was performed to confirm the sequence o...

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Section: Resultsmentioning

confidence: 99%

Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis

Martianov

Brancorsini

Catena

et al. 2005

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

190

168

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“…Synthesis of mouse oocyte histone H4 occurs independently of DNA replication during oogenesis (12), and synthesis of testis-specific histones continues during spermatogenesis, long after DNA synthesis for meiosis has finished (4,39,40). A number of histone H1 proteins are also synthesized independently of DNA replication (11), and H1 mRNAs, particularly H1c and H1e mRNA, are present in nondividing cells (41). The decoupling of DNA and histone synthesis in certain specific cases such as spermatogenesis and oogenesis would seem to support the need for non-chromatin histone storage proteins.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Histone H1-binding Protein, NASP, as a Cell Cycle-regulated Somatic Protein

Richardson¹,

Batova²,

Widgren³

et al. 2000

Journal of Biological Chemistry

134

160

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Nuclear autoantigenic sperm protein (NASP), initially described as a highly autoimmunogenic testis and sperm-specific protein, is a histone-binding protein that is a homologue of the N1/N2 gene expressed in oocytes of Xenopus laevis. Here, we report a somatic form of NASP (sNASP) present in all mitotic cells examined, including mouse embryonic cells and several mouse and human tissue culture cell lines. Affinity chromatography and histone isolation demonstrate that NASP from myeloma cells is complexed only with H1, linker histones. Somatic NASP is a shorter version of testicular NASP (tNASP) with two deletions in the coding region arising from alternative splicing and differs from tNASP in its 5 untranslated regions. We examined the relationship between NASP mRNA expression and the cell cycle and report that in cultures of synchronized mouse 3T3 cells and HeLa cells sNASP mRNA levels increase during Sphase and decline in G 2 , concomitant with histone mRNA levels. NASP protein levels remain stable in these cells but become undetectable in confluent cultures of nondividing CV-1 cells and in nonmitotic cells in various body tissues. Expression of sNASP mRNA is regulated during the cell cycle and, consistent with a role as a histone transport protein, NASP mRNA expression parallels histone mRNA expression. NASP, 1 initially described as a highly autoimmunogenic testis and sperm-specific protein, is present in the nucleus of spermatozoa and spermatogenic cells (1-3), hence the name nuclear autoantigenic sperm protein. Previous studies (4) have demonstrated that human NASP contains three functional histone binding sites: site I (amino acids 116 -127), site II, (amino acids 469 -512), and site III (amino acids 211-244). In vitro, recombinant NASP will bind both linker and core histones (4). 2As a histone-binding protein (4, 5), NASP appears to be a homologue of the N1/N2 gene expressed in oocytes of Xenopus laevis (6 -9) because, in addition to the conserved coding regions, there is an almost 60% identity between the 3Ј untranslated regions of rabbit NASP and Xenopus N1/N2 mRNAs (2). In Xenopus oocytes, the non-chromatin-bound core histones H3 and H4 are associated in a complex with N1/N2 (10, 11), providing a mechanism for the storage of histones for DNA replication in the early embryo. Both mouse (12) and sea urchin oocytes (13) also store histones in a non-chromatin-bound form. Other mammalian histone-binding proteins, for example the nucleosome assembly factor NAP-1 (14 -17), the chromatin assembly factor CAF-1 (18 -21), and the transcription proteins HIRA-HIRIP3 (22), not only bind histones but appear to be important for the assembly of chromatin (19,(23)(24)(25)(26). Consequently NASP may be important not only for both the storage and transport of histones but also for the assembly of chromatin.Here, we report a somatic form of NASP (sNASP) present in almost all tissues examined, including mouse embryonic cells and several mouse and human tissue culture cell lines. Interestingly, an analysis of the histones comp...

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“…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).…”

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confidence: 99%

mentioning

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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The mouse histone H1 genes: gene organization and differential regulation

Cited by 87 publications

References 60 publications

Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis

Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis

Characterization of the Histone H1-binding Protein, NASP, as a Cell Cycle-regulated Somatic Protein

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

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