Role of DNA methylation in stable gene repression

被引:122
作者
Lande-Diner, Laura
Zhang, Jianmin
Ben-Porath, Ittai
Amariglio, Ninette
Keshet, Ilana
Hecht, Merav
Azuara, Veronique
Fisher, Amanda G.
Rechavi, Gideon
Cedar, Howard [1 ]
机构
[1] Hebrew Univ Jerusalem, Sch Med, Dept Cellular Biochem & Human Genet, IL-91120 Jerusalem, Israel
[2] Tel Aviv Univ, Chaim Sheba Med Ctr, Ctr Canc Res, IL-69978 Tel Aviv, Israel
[3] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel
[4] Tel Aviv Univ, Safra Childrens Hosp, IL-69978 Tel Aviv, Israel
[5] Hammersmith Hosp, Lymphocytes Dev Grp, MRC,Sch Med, Clin Sci Ctr,Imperial Coll, London W12 0NN, England
基金
英国医学研究理事会;
关键词
D O I
10.1074/jbc.M607838200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A large fraction of the animal genome is maintained in a transcriptionally repressed state throughout development. By generating viable Dnmt1(-/-) mouse cells we have been able to study the effect of DNA methylation on both gene expression and chromatin structure. Our results confirm that the underlying methylation pattern has a profound effect on histone acetylation and is the major effector of me-H3(K4) in the animal genome. We demonstrate that many methylated genes are subject to additional repression mechanisms that also impact on histone acetylation, and the data suggest that late replication timing may play an important role in this process.
引用
收藏
页码:12194 / 12200
页数:7
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