Zinc Finger Protein ZFP57 Requires Its Co-factor to Recruit DNA Methyltransferases and Maintains DNA Methylation Imprint in Embryonic Stem Cells via Its Transcriptional Repression Domain

	Zinc Finger Protein ZFP57 Requires Its Co-factor to Recruit DNA Methyltransferases and Maintains DNA Methylation Imprint in Embryonic Stem Cells via Its Transcriptional Repression Domain
	Zuo, XP; Sheng, JP; Lau, HT; McDonald, CM; Andrade, M; Cullen, DE; Bell, FT; Iacovino, M; Kyba, M; Xu, GL
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2012
卷号	287 期号:3 页码:2107-2118
通讯作者	Li, XJ (reprint author), Mt Sinai Sch Med, Black Family Stem Cell Inst, Dept Dev & Regenerat Biol, New York, NY 10029 USA.,Xiajun.li@mssm.edu
英文摘要	Previously, we discovered that ZFP57 is a maternal-zygotic effect gene, and it maintains DNA methylation genomic imprint at multiple imprinted regions in mouse embryos. Despite these findings, it remains elusive how DNA methyltransferases are targeted to the imprinting control regions to initiate and maintain DNA methylation imprint. To gain insights into these essential processes in genomic imprinting, we examined how ZFP57 maintains genomic DNA methylation imprint in mouse embryonic stem (ES) cells. Here we demonstrate that the loss of ZFP57 in mouse ES cells led to a complete loss of genomic DNA methylation imprint at multiple imprinted regions, similar to its role in mouse embryos. However, reintroduction of ZFP57 into Zfp57-null ES cells did not result in reacquisition of DNA methylation imprint, suggesting that the memory for genomic imprinting had been lost or altered in Zfp57-null ES cells in culture. Interestingly, ZFP57 and DNA methyltransferases could form complexes in the presence of KAP1/TRIM28/TIF1 beta when co-expressed in COS cells. We also found that the wildtype exogenous ZFP57 but not the mutant ZFP57 lacking the KRAB box that interacts with its co-factor KAP1/TRIM28/TIF1 beta could substitute for the endogenous ZFP57 in maintaining the DNA methylation imprint in ES cells. These results suggest that ZFP57 may recruit DNA methyltransferases to its target regions to maintain DNA methylation imprint, and this interaction is likely facilitated by KAP1/TRIM28/TIF1 beta.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	DE-NOVO METHYLATION ; MAMMALIAN DEVELOPMENT ; EARLY EMBRYOGENESIS ; GENOMIC IMPRINTS ; RNAI SCREEN ; EFFECT GENE ; INSIGHTS ; DNMT3L ; MICE ; MECHANISMS
收录类别	SCI
语种	英语
WOS记录号	WOS:000299321000051
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/567]
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	Zuo, XP,Sheng, JP,Lau, HT,et al. Zinc Finger Protein ZFP57 Requires Its Co-factor to Recruit DNA Methyltransferases and Maintains DNA Methylation Imprint in Embryonic Stem Cells via Its Transcriptional Repression Domain[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(3):2107-2118.
APA	Zuo, XP.,Sheng, JP.,Lau, HT.,McDonald, CM.,Andrade, M.,...&Li, XJ.(2012).Zinc Finger Protein ZFP57 Requires Its Co-factor to Recruit DNA Methyltransferases and Maintains DNA Methylation Imprint in Embryonic Stem Cells via Its Transcriptional Repression Domain.JOURNAL OF BIOLOGICAL CHEMISTRY,287(3),2107-2118.
MLA	Zuo, XP,et al."Zinc Finger Protein ZFP57 Requires Its Co-factor to Recruit DNA Methyltransferases and Maintains DNA Methylation Imprint in Embryonic Stem Cells via Its Transcriptional Repression Domain".JOURNAL OF BIOLOGICAL CHEMISTRY 287.3(2012):2107-2118.