Maternal histone acetyltransferase KAT8 is required for porcine preimplantation embryo development

Abstract

K (lysine) acetyltransferase 8 (KAT8), an acetyltransferase that specifically catalyzes histone H4 lysine 16 acetylation, is critical for key biological processes including cell proliferation and maintenance of genome stability. However, the role of KAT8 during preimplantation development in pigs remains unclear. Results herein showed that KAT8 mRNA is maternally derived and it is required for successful development of early embryos. An abundance of KAT8 transcripts are expressed in oocytes and its abundance continuously decreases throughout meiotic maturation and preimplantation development. In addition, KAT8 expression is insensitive to RNA polymerase II inhibitor after embryonic genome activation, suggesting its maternal origin. The levels of KAT8 mRNA and H4K16 acetylation were effectively knocked down by siRNA microinjection. Knockdown of KAT8 significantly reduced the blastocyst formation rate and total cell number per blastocyst. Analysis of trophectoderm lineage and marker of DNA double-strand breaks revealed that the impaired developmental competence and quality of embryos might be attributed to defects in both the first two lineages development and genome integrity. Taken together, these results demonstrate that maternal KAT8 is indispensible for porcine early embryo development potentially through maintaining the proliferation of the first two lineages and genome integrity.