SETD2 reduction adversely affects the development of mouse early embryos.

Abstract

SET domain-containing protein 2 (SETD2), the protein of regulating trimethylation status of histone H3 at lysine 36 (H3K36), participates in the maintenance of chromatin architecture, transcription elongation, genome stability, and other biological events. However, its function in preimplantation embryos is still obscure. In this study, specific small interfering RNA was employed to investigate the functions of SETD2. We find that deletion of SETD2 results in the developmental delay of mouse early embryos, indicative of the compromised developmental potential. Remarkably, SETD2 knockdown induces the accumulation of the DNA lesions and apoptotic blastomeres in early embryos. In addition, the methylation level of H3K36 is significantly reduced in two-cell embryos depleted of SETD2. In summary, our data indicate that SETD2 maintains genome stability perhaps via regulating trimethylation status of H3K36, consequently controlling the embryo quality. These findings pave the avenue for understanding the cross-talk between epigenome and SETD2 during early embryo development.