ArticleGenetics2026
Distinct functions in fertility and patterns of paternal incorporation of the histone H2A variants HTAS-1 and HTZ-1 in C. elegans.
Article in Genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
As germ cells transform into sperm, the packaging of DNA is critical for transcriptional reprogramming and transmission of paternal genetic and epigenetic information vital for male fitness. Here we investigated the roles in Caenorhabditis elegans spermatogenesis of two histone H2A variants: HTAS-1, a rapidly-evolving sperm-specific paralog, and HTZ-1, an H2A.Z homolog. We show that, in contrast to the ubiquitiously expressed HTZ-1 that is required for germ cell function, HTAS-1 is incorporated late in sperm formation to improve sperm production and development after fertilization. ChIP-seq analysis of sperm chromatin reveals that HTZ-1 and HTAS-1 are incorporated genome-wide but under-represented on the transcriptionally-repressed X chromosome. HTAS-1 incorporates within gene bodies; in contrast, HTZ-1 incorporates at most targets at the promoter, except at those shared with HTAS-1, where it also incorporates in gene bodies. During spermatogenesis, loss of HTAS-1 has modest effects on expression of germline and nongermline genes, which may cumulatively influence sperm production; loss of HTZ-1 results in both increased and decreased expression of mostly germline-expressed genes. In striking contrast, during oogenesis, HTZ-1 loss causes dramatic upregulation of sperm genes, revealing tissue-specific modes of HTZ-1 regulation. Post-fertilization, HTZ-1 is removed in embryos; however, sperm-supplied HTAS-1 is retained and lack of HTAS-1 contributes to developmental delay of htas-1 mutants. Thus, H2A variants have unique incorporation profiles during spermatogenesis, distinct fates postfertilization, and tissue-specific functions in gene expression. Our studies provide evidence for how evolution of sperm-specific chromatin organizing proteins like H2A variants can optimize male fertility, development, and reproductive fitness.
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