MRG15 is required for pre-mRNA splicing and spermatogenesis

Significance Pre-mRNA splicing generates protein diversity, is involved in the regulation of cellular differentiation, and can be epigenetically regulated by histone modifications. Chromatin binding proteins, which recognize histone modifications, recruit splicing regulators to methylated histones around tissue-specific splicing regions and regulate pre-mRNA splicing. However, the interplay of epigenetic factors and the splicing machinery during spermatogenesis remains unclear. Here, we show that epigenetic regulation of pre-mRNA splicing is required for spermatogenesis and male fertility. Thus, novel splicing diversity is important for spermatogenesis, and defects in this system may trigger disease.