CpG Islands Recruit a Histone H3 Lysine 36 Demethylase

被引:240
作者
Blackledge, Neil P. [1 ]
Zhou, Jin C. [1 ]
Tolstorukov, Michael Y. [2 ]
Farcas, Anca M. [1 ]
Park, Peter J. [2 ]
Klose, Robert J. [1 ]
机构
[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
[2] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA
基金
英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;
关键词
CXXC DOMAIN; METHYLATION STATES; TRANSCRIPTION INITIATION; REPRESSES TRANSCRIPTION; DNA METHYLATION; METHYLTRANSFERASE; COMPLEX; PROTEIN; GENOME; GENES;
D O I
10.1016/j.molcel.2010.04.009
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
In higher eukaryotes, up to 70% of genes have high levels of nonmethylated cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over 20 years ago, but there remains little mechanistic evidence to suggest how these enigmatic elements contribute to promoter function, except that they are refractory to epigenetic silencing by DNA methylation. Here we show that CpG islands directly recruit the H3K36-specific lysine demethylase enzyme KDM2A. Nucleation of KDM2A at these elements results in removal of H3K36 methylation, creating CpG island chromatin that is uniquely depleted of this modification. KDM2A utilizes a zinc finger CxxC (ZF-CxxC) domain that preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated, thus constraining KDM2A to nonmethylated CpG islands. These data expose a straightforward mechanism through which KDM2A delineates a unique architecture that differentiates CpG island chromatin from bulk chromatin.
引用
收藏
页码:179 / 190
页数:12
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