Impact of cytosine methylation on DNA binding specificities of human transcription factors

被引：812

作者：

Yin, Yimeng ^{[1
]}

Morgunova, Ekaterina ^{[1
]}

Jolma, Arttu ^{[1
]}

Kaasinen, Eevi ^{[1
]}

Sahu, Biswajyoti ^{[2
]}

Khund-Sayeed, Syed ^{[3
]}

Das, Pratyush K. ^{[2
]}

Kivioja, Teemu ^{[2
]}

Dave, Kashyap ^{[1
]}

Zhong, Fan ^{[1
]}

Nitta, Kazuhiro R. ^{[1
]}

Taipale, Minna ^{[1
]}

Popov, Alexander ^{[4
]}

Ginno, Paul A. ^{[5
]}

Domcke, Silvia ^{[5
,6
]}

Yan, Jian ^{[1
]}

Schubeler, Dirk ^{[5
,6
]}

Vinson, Charles ^{[3
]}

Taipale, Jussi ^{[1
,2
]}

机构：

[1] Karolinska Inst, Dept Med Biochem & Biophys, Div Funct Genom & Syst Biol, SE-14183 Stockholm, Sweden

[2] Univ Helsinki, Genome Scale Biol Program, POB 63, FI-00014 Helsinki, Finland

[3] NCI, Lab Metab, NIH, Room 3128,Bldg 37, Bethesda, MD 20892 USA

[4] European Synchrotron Radiat Facil, F-38043 Grenoble, France

[5] Friedrich Miescher Inst Biomed Res FMI, Maulbeerstr 66, CH-4058 Basel, Switzerland

[6] Univ Basel, Fac Sci, Peterspl 1, CH-4003 Basel, Switzerland

来源：

SCIENCE | 2017年 / 356卷 / 6337期

基金：

芬兰科学院;

关键词：

EMBRYONIC STEM-CELLS; CPG METHYLATION; GENE-EXPRESSION; SEQUENCING DATA; READ ALIGNMENT; RECOGNITION; CHROMATIN; PROTEINS; PROMOTER; DOMAIN;

D O I：

10.1126/science.aaj2239

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family. Structural analysis showed that homeodomain specificity for methylcytosine depends on direct hydrophobic interactions with the methylcytosine 5-methyl group. This study provides a systematic examination of the effect of an epigenetic DNA modification on human TF binding specificity and reveals that many developmentally important proteins display preference for mCpG-containing sequences.

引用

页数：15

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