组蛋白变体macroH2A对组蛋白H4K20甲基化修饰调控的研究

Histone macroH2A, which has a unique macro domain, is a variant of canonical histone H2A. The molecular weight of macroH2A is three times of H2A. Previous studies demonstrated that macroH2A plays an important role in gene silencing/repression during biological processes of development, cell reprogramming and energy metabolism. However，the exact biological function and its underlying molecular mechanism of macroH2A in gene silencing/repression remain largely unknown. In this study, we will mainly focus on how macroH2A participates in the regulation of gene transcription and chromatin structure through modulating H4K20 methylation. In addition, we will study the physiological function and its molecular mechanism of macroH2A in sex chromosome inactivation and pericentromeric heterochromatin during germ cell meiosis. Through this study, we are going to illuminate the molecular mechanisms by which macroH2A taking part in gene silencing/repression in sex chromosome inactivation and pericentromeric heterochromatin formation during germ cell differentiation and meiosis. The results from this research will enhance our understanding of the important function of macroH2A in gene regulation and its molecular mechanisms during the cell differentiation and development.

组蛋白macroH2A是常规组蛋白H2A的一个变体，它具有独特的macro结构域，分子量是常规组蛋白H2A的三倍。研究表明，macroH2A可能通过参与基因沉默，在个体发育、细胞重编程和能量代谢等生命过程中发挥重要作用。但是，macroH2A.Z在基因沉默中的具体生物学功能和作用机制还尚待阐明。本项目主要研究macroH2A如何通过对H4K20甲基化修饰的调控，从而调控基因转录及染色质高级结构的分子机制，并进一步研究macroH2A可能通过介导X染色体失活和异染色质形成在生殖细胞减数分裂过程中的生理功能。通过本项目的研究，我们将从分子及生理水平上阐明macroH2A如何完成其生物学功能，影响细胞命运决定，对于揭示细胞发育分化过程中基因的表达调控及其表观遗传学机理有着重要意义。