组蛋白变体macroH2A调控转录、细胞增殖以及DNA损伤应答等方面，对macroH2A是如何被调节并进入到染色质的机制却尚未明确。已有研究提示nucleolin的沉默引起更高比例的macroH2A-H2B二聚体从染色质解离。我们的前期工作表明nucleolin与macroH2A的表达水平高度相关并且存在相互作用。我们由建模结果推测出nucleolin的N端酸性区域形成潜在的组蛋白结合表面，而实验结果进一步表明了截短该区域会减弱与macroH2A的相互作用。基于此，本项目拟研究nucleolin调控组蛋白变体macroH2A的机制，明确nucleolin对macroH2A结合在染色质水平的调控及其对macroH2A在基因组定位的影响，探究两者的互作机理，以期为探索组蛋白变体如何被置入到染色质及其对功能的影响提供新的思路。

Histone variant macroH2A regulates transcription, cell proliferation and DNA damage responses, but how macroH2A is regulated and assembled into chromatin remains elusive. Previous studies suggest a higher proportion of macroH2A-H2B dimers are mobilized from chromatin in nucleolin-knockdown cells. Our preliminary works indicate that expression level of nucleolin is highly correlated with macroH2A. Furthermore, nucleolin interacts with macroH2A. We identified an N-terminal acidic region of nucleolin that may be important for histone binding based on the modeling. Removing the acidic region, truncated nucleolin showed weaken interaction with macroH2A. Based on aforementioned results, this project intends to study how nucleolin regulates macroH2A. In this proposal, we will analyze how macroH2A's chromatin association regulated by nucleolin and its influence on the genomic distribution of macroH2A, revealing their interaction mechanism. Results of this project will provide novel insights into how histone variants are assembled into chromatin and its effects on function.