Reductions in linker histone levels are tolerated in developing spermatocytes but cause changes in specific gene expression

Qingcong Lin, Amy Inselman, Xing Han, Hui Xu, Weijia Zhang, Mary Ann Handel, Arthur I. Skoultchi

Research output: Contribution to journalArticle

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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 Hla 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.

Original languageEnglish (US)
Pages (from-to)23525-23535
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number22
DOIs
StatePublished - May 28 2004

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Spermatocytes
Gene expression
Germ Cells
Histones
Nucleosomes
Cells
Gene Expression
Genes
Spermatogenesis
Chromatin
Null Lymphocytes
Mammals
Gene Targeting
Gene Silencing
Eukaryotic Cells
Product Packaging
Microarray Analysis
Microarrays
Embryonic Stem Cells
Stem cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Reductions in linker histone levels are tolerated in developing spermatocytes but cause changes in specific gene expression. / Lin, Qingcong; Inselman, Amy; Han, Xing; Xu, Hui; Zhang, Weijia; Handel, Mary Ann; Skoultchi, Arthur I.

In: Journal of Biological Chemistry, Vol. 279, No. 22, 28.05.2004, p. 23525-23535.

Research output: Contribution to journalArticle

Lin, Qingcong ; Inselman, Amy ; Han, Xing ; Xu, Hui ; Zhang, Weijia ; Handel, Mary Ann ; Skoultchi, Arthur I. / Reductions in linker histone levels are tolerated in developing spermatocytes but cause changes in specific gene expression. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 22. pp. 23525-23535.
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