Disease relevance of Hist1h1t

• The binding of all known linker histones, named H1a through H1e, including H1(0) and H1t, to a model chromatin complex based on a DNA fragment containing the mouse mammary tumor virus long terminal repeat promotor was systematically studied [1].
• One phage containing the testis specific mouse H1t histone gene and its flanking regions was isolated [2].

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

• Spermatogenesis proceeds normally in mice without linker histone H1t [6].
• The linker histone subtypes H1.1 and H1t are expressed at high levels in meiotic and early haploid cells [7].
• In this report we have eliminated the single copy H1t gene by homologous recombination from the mouse genome to analyse the function of the H1t protein during spermatogenesis [6].
• In former experiments we have shown that H1.1 and H1.2 histone gene expression is significantly enhanced in testis of adult H1t deficient mice [8].
• The testis-specific histone H1t gene is strongly repressed by a G/C-rich region just downstream of the TATA Box [9].

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

• To disrupt the compensation, we generated H1t and H1a double null mice by two sequential gene-targeting steps in embryonic stem cells [17].
• Northern blot and in situ hybridization has detected H1t mRNA only at the stage of pachytene spermatocytes [12].
• Just a faint H1t band is seen in Western blots of nuclear protein from 9-day-old mice [12].
• In contrast to H1t mRNA, the H1t protein has not been detected in spermatogonia by electron microscopy after immunogold staining [12].
• Northern blot analysis showed that the mouse H1t gene is expressed only in mouse testis at the stage of pachytene spermatocytes and that the H1t mRNA is not polyadenylated [2].

References