The N-terminus of histone H3 is required for de novo DNA methylation in chromatin

	The N-terminus of histone H3 is required for de novo DNA methylation in chromatin
	Hu, JL; Zhou, BO; Zhang, RR; Zhang, KL; Zhou, JQ; Xu, GL
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2009
卷号	106 期号:52 页码:22187-22192
关键词	Dnmt3a Dnmt3L H3K4 methylation PHD domain yeast Saccharomyces cerevisiae Dnmt3L promoter
通讯作者	Zhou, JQ (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,jqzhou@sibs.ac.cn ; glxu@sibs.ac.cn
英文摘要	DNA methylation and histone modification are two major epigenetic pathways that interplay to regulate transcriptional activity and other genome functions. Dnmt3L is a regulatory factor for the de novo DNA methyltransferases Dnmt3a and Dnmt3b. Although recent biochemical studies have revealed that Dnmt3L binds to the tail of histone H3 with unmethylated lysine 4 in vitro, the requirement of chromatin components for DNA methylation has not been examined, and functional evidence for the connection of histone tails to DNA methylation is still lacking. Here, we used the budding yeast Saccharomyces cerevisiae as a model system to investigate the chromatin determinants of DNA methylation through ectopic expression of murine Dnmt3a and Dnmt3L. We found that the N terminus of histone H3 tail is required for de novo methylation, while the central part encompassing lysines 9 and 27, as well as the H4 tail are dispensable. DNA methylation occurs predominantly in heterochromatin regions lacking H3K4 methylation. In mutant strains depleted of H3K4 methylation, the DNA methylation level increased 5-fold. The methylation activity of Dnmt3a largely depends on the Dnmt3L's PHD domain recognizing the histone H3 tail with unmethylated lysine 4. Functional analysis of Dnmt3L in mouse ES cells confirmed that the chromatin-recognition ability of Dnmt3L's PHD domain is indeed required for efficient methylation at the promoter of the endogenous Dnmt3L gene. These findings establish the N terminus of histone H3 tail with an unmethylated lysine 4 as a chromatin determinant for DNA methylation.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	EMBRYONIC STEM-CELLS ; ARGININE METHYLATION ; CATALYTIC-ACTIVITY ; DNMT3L ; METHYLTRANSFERASE ; LYSINE-4 ; PROTEIN ; FAMILY ; G9A ; HETEROCHROMATIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000273178700029
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1301]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Hu, JL,Zhou, BO,Zhang, RR,et al. The N-terminus of histone H3 is required for de novo DNA methylation in chromatin[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2009,106(52):22187-22192.
APA	Hu, JL,Zhou, BO,Zhang, RR,Zhang, KL,Zhou, JQ,&Xu, GL.(2009).The N-terminus of histone H3 is required for de novo DNA methylation in chromatin.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,106(52),22187-22192.
MLA	Hu, JL,et al."The N-terminus of histone H3 is required for de novo DNA methylation in chromatin".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106.52(2009):22187-22192.