PHCF1调节哺乳物细胞组成型异染色质的功能和机制研究

异染色质通过形成紧致的染色质高级结构来维持转录沉默状态。存在于近着丝粒区域等基因组重复序列上的组成型异染色质，在保证有丝分裂中染色体的正常分离以及维持转座子的沉默等过程中发挥重要作用，是维持基因组完整性所必需的。异染色质结构的异常与癌症和衰老等疾病的密切相关。目前对于异染色质建立和维持机制的了解主要来自对裂殖酵母等模式生物的研究，而哺乳动物细胞组成型异染色质的调节机制还有待深入研究。在前期工作中通过一个在细胞中进行的RNAi的高通量筛选实验，我们发现PHCF1是一个此前未知的组成型异染色质的调节因子。本项目拟对PHCF1调节异染色质的功能和分子机制开展研究。

Heterochromatin forms condensed high-order chromatin structure to maintain transcription silencing. Highly concentrated at repetitive genomic sequences such as pericentromeric regions, the constitutive heterochromatin plays an essential role in maintaining the genome integrity, including safeguarding the chromosome segregation during meitotic cell division and transposon silencing. The current understanding of the establishment and maintenance of heterochromatin are mainly based on the study of model organisms like fission yeast, while the regulation mechanisms of mammalian constitutive heterochromatin remain to be further explored. Based on a high-throughput RNAi screening in HeLa cells, we identified PHCF1 as a novel regulator of the mammalian constitutive heterochromatin.In this project, we propose to study the function and molecular mechanism of PHCF1 in regulating heterochromatin.