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Impact of cytosine methylation on DNA binding specificities of human transcription factors.
Journal article

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

  • Yin Y Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Morgunova E Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Jolma A Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Kaasinen E Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Sahu B Genome-Scale Biology Program, Post Office Box 63, FI-00014 University of Helsinki, Helsinki, Finland.
  • Khund-Sayeed S Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Room 3128, Building 37, Bethesda, MD 20892, USA.
  • Das PK Genome-Scale Biology Program, Post Office Box 63, FI-00014 University of Helsinki, Helsinki, Finland.
  • Kivioja T Genome-Scale Biology Program, Post Office Box 63, FI-00014 University of Helsinki, Helsinki, Finland.
  • Dave K Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Zhong F Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Nitta KR Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Taipale M Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Popov A European Synchrotron Radiation Facility, 38043 Grenoble, France.
  • Ginno PA Friedrich-Miescher-Institute for Biomedical Research (FMI), Maulbeerstrasse 66, 4058 Basel, Switzerland.
  • Domcke S Friedrich-Miescher-Institute for Biomedical Research (FMI), Maulbeerstrasse 66, 4058 Basel, Switzerland.
  • Yan J Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden.
  • Schübeler D Friedrich-Miescher-Institute for Biomedical Research (FMI), Maulbeerstrasse 66, 4058 Basel, Switzerland.
  • Vinson C Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Room 3128, Building 37, Bethesda, MD 20892, USA.
  • Taipale J Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 141 83 Stockholm, Sweden. jussi.taipale@ki.se.
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  • 2017-05-06
Published in:
  • Science (New York, N.Y.). - 2017
CpG Islands
Cytosine
DNA
DNA Methylation
Dinucleoside Phosphates
Epigenesis, Genetic
Genome, Human
Humans
Protein Binding
Protein Domains
SELEX Aptamer Technique
Transcription Factors
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/53637
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