The effects of cytosine methylation on general transcription factors

doi:10.1038/srep29119

CORC > 北京大学 > 化学与分子工程学院

	The effects of cytosine methylation on general transcription factors
	Jin, Jianshi ; Lian, Tengfei ; Gu, Chan ; Yu, Kai ; Gao, Yi Qin ; Su, Xiao-Dong
刊名	SCIENTIFIC REPORTS
	2016
关键词	GERM-CELL DEVELOPMENT NON-CPG METHYLATION DNA-METHYLATION GLUCOCORTICOID-RECEPTOR BASE-RESOLUTION STACKING INTERACTIONS RETT-SYNDROME BINDING GENOME RECOGNITION
DOI	10.1038/srep29119
英文摘要	DNA methylation on CpG sites is the most common epigenetic modification. Recently, methylation in a non-CpG context was found to occur widely on genomic DNA. Moreover, methylation of non-CpG sites is a highly controlled process, and its level may vary during cellular development. To study non-CpG methylation effects on DNA/protein interactions, we have chosen three human transcription factors (TFs): glucocorticoid receptor (GR), brain and muscle ARNT-like 1 (BMAL1) - circadian locomotor output cycles kaput (CLOCK) and estrogen receptor (ER) with methylated or unmethylated DNA binding sequences, using single-molecule and isothermal titration calorimetry assays. The results demonstrated that these TFs interact with methylated DNA with different effects compared with their cognate DNA sequences. The effects of non-CpG methylation on transcriptional regulation were validated by cell-based luciferase assay at protein level. The mechanisms of non-CpG methylation influencing DNA-protein interactions were investigated by crystallographic analyses and molecular dynamics simulation. With BisChIP-seq assays in HEK-293T cells, we found that GR can recognize highly methylated sites within chromatin in cells. Therefore, we conclude that non-CpG methylation of DNA can provide a mechanism for regulating gene expression through directly affecting the binding of TFs.; National Natural Science Foundation of China [31170710, 31270803, 21125311, 91027044, U1430237]; National Basic Research Program of China (973 Program) [2011CB911103, 2012CB917304]; Peking University 985 grant; Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences; SCI(E); PubMed; ARTICLE; gaoyq@pku.edu.cn; xdsu@pku.edu.cn; 29119; 6
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/491962]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Jin, Jianshi,Lian, Tengfei,Gu, Chan,et al. The effects of cytosine methylation on general transcription factors[J]. SCIENTIFIC REPORTS,2016.
APA	Jin, Jianshi,Lian, Tengfei,Gu, Chan,Yu, Kai,Gao, Yi Qin,&Su, Xiao-Dong.(2016).The effects of cytosine methylation on general transcription factors.SCIENTIFIC REPORTS.
MLA	Jin, Jianshi,et al."The effects of cytosine methylation on general transcription factors".SCIENTIFIC REPORTS (2016).