2. Academic Validation
  3. Impact of cytosine methylation on DNA binding specificities of human transcription factors

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

  • Science. 2017 May 5;356(6337):eaaj2239. doi: 10.1126/science.aaj2239.
Yimeng Yin 1,  Ekaterina Morgunova 1,  Arttu Jolma 1,  Eevi Kaasinen 1,  Biswajyoti Sahu 2,  Syed Khund-Sayeed 3,  Pratyush K Das 2,  Teemu Kivioja 2,  Kashyap Dave 1,  Fan Zhong 1,  Kazuhiro R Nitta 1,  Minna Taipale 1,  Alexander Popov 4,  Paul A Ginno 5,  Silvia Domcke 5 6,  Jian Yan 1,  Dirk Schübeler 5 6,  Charles Vinson 3,  Jussi Taipale 7 2
Affiliations

Affiliations

  • 1 Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • 2 Genome-Scale Biology Program, Post Office Box 63, FI-00014 University of Helsinki, Helsinki, Finland.
  • 3 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Room 3128, Building 37, Bethesda, MD 20892, USA.
  • 4 European Synchrotron Radiation Facility, 38043 Grenoble, France.
  • 5 Friedrich-Miescher-Institute for Biomedical Research (FMI), Maulbeerstrasse 66, 4058 Basel, Switzerland.
  • 6 Faculty of Science, University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
  • 7 Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden. jussi.taipale@ki.se.
PMID: 28473536 DOI: 10.1126/science.aaj2239
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.

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