The Role Of Histone Chaperone ASF1A During Oocyte Maturation And Early Embryonic Development In Mice

Anti-Silencing Factor 1(ASF1)is a histone chaperone for histones H3 and H4,which regulate chromatin dynamics through its nucleosome assembly and disassembly activity.ASF1 is involved in various biological processes such as DNA replication,DNA damage repair,genomic reprogramming,cell proliferation and cell senescence.In mammalian species,there are two paralogs of ASF1,ASF1 A and ASF1 B.It was reported that ASF1 B is mainly involved in cell proliferation and plays an important role during early embryonic development.However,the function and mechanism of ASF1 A during oocyte maturation and early embryonic development remain mostly elusive.In this study,we took advantage of the specifically synthesized ASF1A-Morpholino to knock down ASF1 A in oocytes and early embryos to explore its role in oocyte maturation and early embryo development.Knockdown of ASF1 A in GV stage oocytes did not affect neither the formation of spindle during the first meiosis nor the oocytes maturation.When ASF1 A was knocked down in the fertilized oocytes,the deposition of histone H3.3 in the male pronucleus was largely decreased and hindered preimplantation embryo development.Knockdown of ASF1 A in fertilized oocytes significantly reduced the level of H3K56 ac and the expression of Oct4 and PCNA in the Blastocyst stage embryos,and led to accumulation of DNA damage.These result collectively suggested that ASF1 A plays an important role during preimplantation embryos development through regulating histone H3.3 deposition in the male pronucleus,maintaining the level of H3K56 ac and expression of Oct4 and PCNA,and preventing accumulation of DNA damage in the preimplantation embryos in mice.