Abstract
Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages ofspermatogenesis. H3t gene deficiency leads to azoospermia because of the loss of haploid germ cells. When differentiating spermatogonia emerge in normal spermatogenesis, H3t appears and replaces the canonical H3 proteins. Structural and biochemical analyses reveal that H3t-containing nucleosomes are more flexible than the canonical nucleosomes. Thus, by incorporating H3t into the genome during spermatogonial differentiation, male germ cells are able to enter meiosis and beyond.
Highlights
When stem cells are committed to enter certain cell lineages, they undergo epigenetic and chromatin remodeling to acquire unique genomic structures that ensure the stability of their fate
H3t Deficiency Leads to Male Infertility in Mice We first analyzed the expression pattern of H3t in various tissues on the FANTOM5 mouse promoterome database deposited in ZENBU (Table S1), confirmed its expression by qRT-PCR amplified with primer sets designed from 50 cap analysis of gene expression (CAGE) and 30-sequence data (Figures S1A and S1B) (Maehara et al, 2015)
Both male and female knockout mice were viable and healthy, the male mice turned out to be sterile (Figures 1B, S1G, and S1H). In line with this phenotype, H3t null mice had strikingly smaller testes compared with wild-type and heterozygous knockout mice (Figures 1C and S1I)
Summary
When undifferentiated spermatogonia enter differentiation, they go through meiotic recombination followed by histone-protamine transition, eventually to become highly specialized haploid cells called spermatozoa. Ueda et al reveal a testis-specific histone variant H3t that enables nucleosomes to form an open chromatin structure and is essential for the initial step of spermatogenesis. Highlights d H3t is essential for spermatogenesis, and loss leads to azoospermia. 5B1L 5B1M d H3t is expressed in differentiating spermatogonia but lost from spermatozoa d H3t is required for spermatogonial differentiation and ensures entry into meiosis d H3t-containing nucleosomes form an open chromatin structure. 2017, Cell Reports 18, 593–600 January 17, 2017 a 2017 The Author(s).
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