The histone methyltransferase SETD2 is required for expression of acrosin-binding protein 1 and protamines and essential for spermiogenesis in mice.

摘要: Spermatogenesis is precisely controlled by complex gene expression programs and involves epigenetic reprogramming, including histone modification DNA methylation. SET domain–containing 2 (SETD2) the predominant methyltransferase catalyzing trimethylation of H3 lysine 36 (H3K36me3) plays key roles in embryonic stem cell differentiation somatic development. However, its role male germ development remains elusive. Here, we demonstrate an essential Setd2 for spermiogenesis, final stage spermatogenesis. Using RNA-seq, found that, postnatal mouse testes, mRNA levels dramatically increase 14-day-old mice. a cell–specific knockout model, also that targeted cells causes aberrant spermiogenesis with acrosomal malformation before step 8 round-spermatid stage, resulting complete infertility. Furthermore, noted deficiency results loss H3K36me3 significantly decreases thousands genes, those encoding acrosin-binding protein 1 (Acrbp1) protamines, required Our findings thus reveal previously unappreciated SETD2-dependent provide clues to molecular mechanisms disorders underlying