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Gene Review

Hist1h1t  -  histone cluster 1, H1t

Mus musculus

Synonyms: H1.6, H1ft, H1t, Histone H1t, Testicular H1 histone
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Disease relevance of Hist1h1t


High impact information on Hist1h1t

  • Mice contain at least seven nonallelic subtypes of H1, including the somatic variants H1a through H1e, the testis-specific variant H1t, and the replacement linker histone H1(0) [3].
  • 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 [4].
  • To investigate the role of H1t in spermatogenesis, we disrupted the H1t gene by homologous recombination in mouse embryonic stem cells [4].
  • 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 [4].
  • The entire cluster contains six histone H1 genes, including the testis-specific histone H1t gene that maps to the middle of the cluster [5].

Biological context of Hist1h1t


Anatomical context of Hist1h1t

  • The histone gene Hist1h1t is expressed exclusively in spermatocytes and may have a function in establishing an open chromatin structure for the replacement of histones by transition proteins and protamines [10].
  • The histone gene H1t is expressed exclusively in pachytene spermatocytes of the testis [6].
  • Mice homozygous for the mutation and completely lacking H1t protein in their germ cells were fertile and showed no detectable defect in spermatogenesis [4].
  • Mutation of TE1 leads to a drop in H1t promoter activity in germinal GC-2spd cells as well as in nongerminal Leydig, NIH3T3, and C127I cell lines [11].
  • We have extended this analysis to more sensitive approaches and demonstrate, by RNase protection and electron-microscopic in situ hybridization, that H1t mRNA is detectable even in spermatogonia [12].

Associations of Hist1h1t with chemical compounds

  • Fusions between various upstream fragments of the H1t gene and the chloramphenicol acetyltransferase-encoding reporter gene were analyzed in mouse L cells by both transient and permanent transfection [13].
  • These results suggest that cytosine methylation may contribute to the transcriptional silencing of the testis-specific histone H1t gene in nonexpressing tissues such as liver [14].
  • Polyacrylamide gel electrophoresis of products formed in a reticulocyte lysate-dependent cell-free translation system has enabled identification of histone variants, H1t, H2S, H2A . X, an H4-like protein and a low Mr protein (presumably TP and/or protamine) [15].

Regulatory relationships of Hist1h1t

  • The rat histone H1d gene has intragenic activating sequences that are absent from the testis-specific variant H1t [16].

Other interactions of Hist1h1t

  • Therefore, in these cells, H1t seems not to be replaced by H1.1 or H1.2 [8].
  • In this report we have quantified the mRNA of different H1 genes in 9-day- and 20-day-old wild type and H1t knock out mice [8].
  • To form aggregates with the histones H1t and H1b, however, greater amounts of protein were required [1].
  • In this system the wild type H1d promoter was 20-fold stronger than the H1t promoter [9].

Analytical, diagnostic and therapeutic context of Hist1h1t


  1. In vitro binding of H1 histone subtypes to nucleosomal organized mouse mammary tumor virus long terminal repeat promotor. Talasz, H., Sapojnikova, N., Helliger, W., Lindner, H., Puschendorf, B. J. Biol. Chem. (1998) [Pubmed]
  2. Structure and expression of the mouse testicular H1 histone gene (H1t). Drabent, B., Bode, C., Doenecke, D. Biochim. Biophys. Acta (1993) [Pubmed]
  3. Mice develop normally without the H1(0) linker histone. Sirotkin, A.M., Edelmann, W., Cheng, G., Klein-Szanto, A., Kucherlapati, R., Skoultchi, A.I. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. Normal spermatogenesis in mice lacking the testis-specific linker histone H1t. Lin, Q., Sirotkin, A., Skoultchi, A.I. Mol. Cell. Biol. (2000) [Pubmed]
  5. Characterization of the mouse histone gene cluster on chromosome 13: 45 histone genes in three patches spread over 1Mb. Wang, Z.F., Krasikov, T., Frey, M.R., Wang, J., Matera, A.G., Marzluff, W.F. Genome Res. (1996) [Pubmed]
  6. Spermatogenesis proceeds normally in mice without linker histone H1t. Drabent, B., Saftig, P., Bode, C., Doenecke, D. Histochem. Cell Biol. (2000) [Pubmed]
  7. Triple knockouts reveal gene interactions affecting fertility of male mice. Nayernia, K., Drabent, B., Meinhardt, A., Adham, I.M., Schwandt, I., Müller, C., Sancken, U., Kleene, K.C., Engel, W. Mol. Reprod. Dev. (2005) [Pubmed]
  8. Histone H1t is not replaced by H1.1 or H1.2 in pachytene spermatocytes or spermatids of H1t-deficient mice. Drabent, B., Benavente, R., Hoyer-Fender, S. Cytogenet. Genome Res. (2003) [Pubmed]
  9. The testis-specific histone H1t gene is strongly repressed by a G/C-rich region just downstream of the TATA Box. Clare, S.E., Fantz, D.A., Kistler, W.S., Kistler, M.K. J. Biol. Chem. (1997) [Pubmed]
  10. Synergistic effects of germ cell expressed genes on male fertility in mice. Nayernia, K., Meinhardt, A., Drabent, B., Adham, I.M., Müller, C., Steckel, M., Sancken, U., Engel, W. Cytogenet. Genome Res. (2003) [Pubmed]
  11. TE2 and TE1 sub-elements of the testis-specific histone H1t promoter are functionally different. Wilkerson, D.C., Wolfe, S.A., Grimes, S.R. J. Cell. Biochem. (2003) [Pubmed]
  12. Expression of the mouse histone gene H1t begins at premeiotic stages of spermatogenesis. Drabent, B., Bode, C., Miosge, N., Herken, R., Doenecke, D. Cell Tissue Res. (1998) [Pubmed]
  13. Analysis of the promoter for the gene encoding the testis-specific histone H1t in a somatic cell line: evidence for cell-cycle regulation and modulation by distant upstream sequences. Kremer, E.J., Kistler, W.S. Gene (1992) [Pubmed]
  14. Testis-specific histone H1t gene is hypermethylated in nongerminal cells in the mouse. Singal, R., vanWert, J., Bashambu, M., Wolfe, S.A., Wilkerson, D.C., Grimes, S.R. Biol. Reprod. (2000) [Pubmed]
  15. Histone messenger RNAs of the mouse testis. Faulkner, R.D., Whisenant, E.C., Bhatnagar, Y.M. Biochem. Biophys. Res. Commun. (1986) [Pubmed]
  16. The rat histone H1d gene has intragenic activating sequences that are absent from the testis-specific variant H1t. Horvath, G.C., Dasgupta, A., Kistler, M.K., Kistler, W.S. Biochim. Biophys. Acta (2003) [Pubmed]
  17. Reductions in linker histone levels are tolerated in developing spermatocytes but cause changes in specific gene expression. Lin, Q., Inselman, A., Han, X., Xu, H., Zhang, W., Handel, M.A., Skoultchi, A.I. J. Biol. Chem. (2004) [Pubmed]
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