The molecular mechanism underlying epigenetic inheritance remains largely unknown. Previous studies have shown that transmission of paternal acquired traits through the male germline (i.e., sperm) requires functional DNMT2 to maintain normal profiles of sperm-borne tRNA-derived small RNAs (tsRNAs). Here we report that maternal transmission of a Kit paramutant phenotype (white tail tip) through the female germline (i.e., oocytes) also requires normal function of DNMT2 and normal profiles of DNMT2-dependent tsRNAs and other small noncoding RNAs (sncRNAs) in sperm. Specifically, ablation of DNMT2 leads to aberrant profiles of tsRNAs and other sncRNAs in sperm, which correlate with drastically dysregulated mRNA transcriptome in pronuclear zygotes derived from oocytes carrying the Kit paramutation and a complete blockage of transmission of the paramutant phenotype through the oocytes. Together with previous reports, the present study suggests that both paternal and maternal transmission of epigenetic phenotypes requires DNMT2-dependent tsRNAs in sperm.

Maternal transmission of a paramutant phenotype requires intact DNMT2 functions in the male germline