GSE108717
Setd2-dependent H3K36me3 is required for Acrbp1 and protamine transcriptions and spermiogenesis in mice
Spermatogenesis is precisely cotrolled by complex gene expression programs and involves epigenetic reprogramming including histone modification and DNA methylation. Setd2 catalyzes the trimethylation of histone H3 Lys36 (H3K36me3) and plays key roles in embryonic stem cell differentiation and somatic cell development; however, its role in male germ cell development remains elusive. Here we demonstrate an essential role of Setd2 for spermiogenesis. We show that targeted knockout of Setd2 in germ cells causes aberrant spermiogenesis with acrosomal malformation before step 8 round spermatid stage, resulting in complete male infertile. Furthermore, we show a complete loss of H3K36me3 and a significant altered gene expression profile, including Acrbp1 and protamines, caused by Setd2 deficiency. Our findings reveal a previously underappreciated role of Setd2-dependent H3K36me3 for spermiogenesis and improved the understanding of epigenetic disorders underlying male infertility. Overall design: We examined H3K36me3 and transcriptomes in in PD and RS cells upon Setd2 loss.