Maternal histone acetyltransferase KAT8 is required for porcine preimplantation embryo development.

Zubing Cao,Di Gao,Lei Luo,Yunsheng Li,Yunhai Zhang,Tengteng Xu,Ronghua Wu,Jianyong Han

doi:10.18632/oncotarget.21657

Zubing Cao, Di Gao + Show 6 more

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https://doi.org/10.18632/oncotarget.21657

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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.

Highlights

The pig is an economically important farm animal in agriculture, and a considerably better animal model for human disease in biomedicine [1]
A genomic database query revealed that the pig KAT8 (pKAT8) gene contains 11 exons separated by 10 introns and is located at chromosome 3, spanning over 10.9 kb in length (Figure 1B)
In the present study our results reveal an important role of maternally provided histone acetyltransferase K (lysine) acetyltransferase 8 (KAT8) in porcine preimplantation embryos

Summary

Introduction

The pig is an economically important farm animal in agriculture, and a considerably better animal model for human disease in biomedicine [1]. The demands of the over-expanding world population for genetically modified pigs with either superior economic traits or human disease state have been increasing. The preimplantation developmental competence of porcine embryos derived from IVP is extremely poor [3]. To improve developmental efficiency of porcine embryos, we have to fully understand molecular mechanisms that regulate porcine preimplantation embryo development. A growing body of evidence strongly shows that maternally derived gene products including transcription factors www.impactjournals.com/oncotarget and epigenetic modifiers tightly regulate these cellular and molecular events in mammalian preimplantation embryos [4]. Previous studies indicate that some maternal-effect genes are involved in the regulation of preimplantation embryo development in mice [5,6,7] and pigs [8, 9]. Maternally provided BCAS2 knockout embryos exhibited severe developmental defects mainly because of the accumulation of DNA double-strand breaks [10]

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