Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter

	Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter
	Chen, H; Kazemier, HG; de Groote, ML; Ruiters, MHJ; Xu, GL; Rots, MG
刊名	NUCLEIC ACIDS RESEARCH
	2014
卷号	42 期号:3 页码:1563-1574
通讯作者	Rots, MG (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Med Biol, Hanzeplein1, NL-9713 GZ Groningen, Netherlands.,M.G.Rots@umcg.nl
英文摘要	Increasing evidence indicates that active DNA demethylation is involved in several processes in mammals, resulting in developmental stage-specificity and cell lineage-specificity. The recently discovered Ten-Eleven Translocation (TET) dioxygenases are accepted to be involved in DNA demethylation by initiating 5-mC oxidation. Aberrant DNA methylation profiles are associated with many diseases. For example in cancer, hypermethylation results in silencing of tumor suppressor genes. Such silenced genes can be re-expressed by epigenetic drugs, but this approach has genome-wide effects. In this study, fusions of designer DNA binding domains to TET dioxygenase family members (TET1, -2 or -3) were engineered to target epigenetically silenced genes (ICAM-1, EpCAM). The effects on targeted CpGs' methylation and on expression levels of the target genes were assessed. The results indicated demethylation of targeted CpG sites in both promoters for targeted TET2 and to a lesser extent for TET1, but not for TET3. Interestingly, we observed re-activation of transcription of ICAM-1. Thus, our work suggests that we provided a mechanism to induce targeted DNA demethylation, which facilitates re-activation of expression of the target genes. Furthermore, this Epigenetic Editing approach is a powerful tool to investigate functions of epigenetic writers and erasers and to elucidate consequences of epigenetic marks.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	ARTIFICIAL TRANSCRIPTION FACTORS ; PATERNAL GENOME ; ACTIVE-DEMETHYLATION ; EPIGENETIC MARKS ; GENE-EXPRESSION ; OVARIAN-CANCER ; MAMMALIAN DNA ; HUMAN-DISEASE ; TET PROTEINS ; METHYLATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000331138800019
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/166]
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	Chen, H,Kazemier, HG,de Groote, ML,et al. Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter[J]. NUCLEIC ACIDS RESEARCH,2014,42(3):1563-1574.
APA	Chen, H,Kazemier, HG,de Groote, ML,Ruiters, MHJ,Xu, GL,&Rots, MG.(2014).Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter.NUCLEIC ACIDS RESEARCH,42(3),1563-1574.
MLA	Chen, H,et al."Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter".NUCLEIC ACIDS RESEARCH 42.3(2014):1563-1574.