| Literature DB >> 28473536 |
Yimeng Yin1, Ekaterina Morgunova1, Arttu Jolma1, Eevi Kaasinen1, Biswajyoti Sahu2, Syed Khund-Sayeed3, Pratyush K Das2, Teemu Kivioja2, Kashyap Dave1, Fan Zhong1, Kazuhiro R Nitta1, Minna Taipale1, Alexander Popov4, Paul A Ginno5, Silvia Domcke5,6, Jian Yan1, Dirk Schübeler5,6, Charles Vinson3, Jussi Taipale7,2.
Abstract
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.Entities:
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Year: 2017 PMID: 28473536 PMCID: PMC8009048 DOI: 10.1126/science.aaj2239
Source DB: PubMed Journal: Science ISSN: 0036-8075 Impact factor: 47.728