Regulation Of Acetylation Of Histone H4 Lysine 12 And Phosphorylation Of Histone H3 Serine 10 By HDACs During Mouse Oocyte Meiosis

Regulation in histone modifications is essential to chromatin structure and gene expression during mitosis and lower animals' meiosis. Resaerches about histone modifications in mammalian oocytes during meiosis focused on the individual modification, but the regulation mechanisms of different histone modifications were rarely reported. As known, acetylation and phosphorylation of hitstone were crucial to oocyte during meitic maturation, in this study we investigated the acetylation and phosphorylation of hitstone in meiotic oocytes under the influence of broad-spectrum inhibitior and specific inhibitor of HDACs (histone dacetylases). Then, we turn to confirm which HDACs play roles in histone phosphorylation and whether HDACs regulated the histone phosphorylation by Aurora kinases. However, the results provided reference to molecular mechanism in histone modification.1?Part ?:Regulation of histone acetylation and its effects on maturation quality during mouse oocyte meiosisThe objective of this study was to understand the regulation mechanism of histone acetylation during oocyte meiosis. Using the acetylation of histone H4 at lysine 12 as a indicator, we explored the regulation of histone acetylation and its effects on mouse oocytes maturation quality. The results of the present study demonstrated that histone acetylated in germinal vesicle (GV) oocytes and deacetylated in metaphase ? (MI) and metaphase ? (M ?)oocytes; class ? HDACs regulated the histone acetylation during meiosis; dynamic changes in histone acetylation/deacetylation occurred during meiosis; an increased levels of histone acetylation by specific inhibition of HDACs had no effect on rates of oocytes maturation, spindle morphology and chromosome alignment, however, inhibition of HDACs with broad-spectrum inhibitor induced changes in chromosome alignment. Taken together, the results would be very important and useful to investigate the molecular mechanism of histone modifications and improve the efficiency of in vitro production of mammalian embryos.2?Part ?:Regulation of histone phosphorylation by HDACs during mouse oocyte meiosisHistone modifications and the regulation between themselves were essential to mitosis and meiosis. Researches about histone modifications in mammalian oocytes during meiosis focused on the individual modification, but the regulation mechanisms of different histone modifications were rarely reported, and the mechanism about interaction of different histone modification is unknown. We used the phosphorylation of histone H3 at serine 10 and acetylation of histone H4 at lysine 12 as indicators respectively. Firstly, we treated (GV and M?)oocytes with broad-spectrum inhibitor and specific inhibitor of HDACs and investigated the changes in histone acetylation and phosphorylation. We confirmed that histone acetylation could regulate phosphorylation of histone. Then, we examined the changes of mRNA level and protein level after histone phosphorylation kinases activity was suppressed, in order to confirm the regulation of histone phosphorylation by HDACs during oocyte meiosis. The result indicated that the interaction between acetylation and phosphorylation during meiosis was existed, and this interaction was stage-specific during meiosis. Either acetylation of histone H4 at lysine 12 or phosphorylation of histone H3 at serine 10 were regulated by class I HDACs in GV oocytes. But in M? oocytes, class II HDACs regulated the acetylation of histone H4 at lysine 12 or phosphorylation of histone H3 at serine 10. In GV oocytes, neither transcriptional level nor protein level was changed in Aurora-A and Aurora-B, but the transcriptional and protein level of Aurora-C were increased obviously. When the activity of HDAs in M? oocytes was suppressed, neither mRNA level nor protein level was changed in three kinds of Aurora kinases, but the phosphorylation of this three kinds of Aurora kinases was increased obviously. Taken together, the stage-specific regulation between acetylation and phosphorylation during meiosis was existed. In GV oocytes, class I HDACs increased transcriptional level and protein level of Aurora-C, and then promote the phosphorylation of H3S10,but in M? oocytes, phosphorylation of H3S10 was regulated by phosphorylation of Aurora kinases, and class II HDACs play roles in this process. However, the results would as a reference to molecular mechanism in histone modification.