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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Yimeng Yin
  • Ekaterina Morgunova
  • Arttu Jolma
  • Eevi Kaasinen
  • Biswajyoti Sahu
  • Syed Khund-Sayeed
  • Pratyush K. Das
  • Teemu Kivioja
  • Kashyap Dave
  • Fan Zhong
  • Kazuhiro R. Nitta
  • Minna Taipale
  • Alexander Popov
  • Paul A. Ginno
  • Silvia Domcke
  • Dirk Schübeler
  • Charles Vinson
  • Jussi Taipale

Detail(s)

Original languageEnglish
Article numbereaaj2239
Journal / PublicationScience
Volume356
Issue number6337
Publication statusPublished - 5 May 2017
Externally publishedYes

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.

Citation Format(s)

Impact of cytosine methylation on DNA binding specificities of human transcription factors. / Yin, Yimeng; Morgunova, Ekaterina; Jolma, Arttu; Kaasinen, Eevi; Sahu, Biswajyoti; Khund-Sayeed, Syed; Das, Pratyush K.; Kivioja, Teemu; Dave, Kashyap; Zhong, Fan; Nitta, Kazuhiro R.; Taipale, Minna; Popov, Alexander; Ginno, Paul A.; Domcke, Silvia; Yan, Jian; Schübeler, Dirk; Vinson, Charles; Taipale, Jussi.

In: Science, Vol. 356, No. 6337, eaaj2239, 05.05.2017.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal