Abstract
H1 linker histones are involved in packaging chromatin into 30-nm fibers and higher order structures. Most eukaryotic cells contain nearly one H1 molecule for each nucleosome core particle. Male germ cells in mammals contain large amounts of a germ cell-specific linker histone, HIST1HT, herein denoted H1t, which is particularly abundant in pachytene spermatocytes. Despite its abundance in male germ cells and significant divergence in primary sequence from other H1 subtypes, inactivation of the H1t gene in mice showed that it is not required for spermatogenesis. Analysis of germ cell chromatin from H1t null mice showed that other H1 subtypes, especially the testis-enriched HIST1H1A, herein denoted as the H1a subtype, were able to compensate for the absence of H1t to maintain a normal total H1 to nucleosome core ratio. To disrupt the compensation, we generated H1t and H1a double null mice by two sequential gene-targeting steps in embryonic stem cells. Elimination of both H1t and H1a led to a 25% decrease in the ratio of H1 to nucleosome cores in double null germ cells. Surprisingly, the reduction in H1 did not perturb spermatogenesis or produce detectable defects in meiotic processes. Microarray analysis of gene expression showed that the reduced linker histone levels did not affect global gene expression, but it did cause changes in expression of specific genes. Our results indicate that a partial reduction in linker histone-nucleosome core particle stoichiometry is tolerated in developing male germ cells.
Highlights
A general feature of histone proteins is that their amino acid sequences are conserved
To disrupt the com- organization of the genes encoding the H1 subtypes appears to pensation, we generated H1t and H1a double null mice be very similar in humans and mice [6, 7]
Our results indicate that a partial reduction in linker histone-nucleosome core particle stoichiometry is tolerated in developing male germ cells
Summary
A general feature of histone proteins is that their amino acid sequences are conserved. In mice eight H1 subtypes have been described [4, 5], including the “somatic” subtypes H1a through H1e, the replacement subtype H1FO (here H1o), the oocyte-specific H1FOO, here denoted as H1oo, and the testis-specific H1t These subtypes are present in humans, and the genomic total H1 to nucleosome core ratio. By two sequential gene-targeting steps in embryonic all of the mouse H1 subtypes have the basic tristem cells. Elimination of both H1t and H1a led to a 25% decrease in the ratio of H1 to nucleosome cores in double null germ cells. Our results indicate that a partial reduction in linker histone-nucleosome core particle stoichiometry is tolerated in developing male germ cells. The most likely explanation for the absence of a phenotype in these single H1 null animals is that
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