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

作者：Yimeng Yin, Ekaterina Morgunova, Arttu Jolma, Eevi Kaasinen, Biswajyoti Sahu, Syed Khund-Sayeed, Pratyush Kumar Das, Teemu Kivioja, Kashyap Dave, Fan Zhong, Kazuhiro R. Nitta, Minna Taipale, А. Н. Попов, Paul A. Ginno, Silvia Domcke, Jian Yan, Dirk Schübeler, Charles Vinson, Jussi Taipale · 发表于：Science · 年份：2017 · DOI：10.1126/science.aaj2239 · 被引用次数：1361 · 研究领域：Epigenetics and DNA Methylation、Genomics and Chromatin Dynamics、Cancer-related gene regulation

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.