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

Author:

Yin Yimeng1ORCID,Morgunova Ekaterina1ORCID,Jolma Arttu1ORCID,Kaasinen Eevi1,Sahu Biswajyoti2ORCID,Khund-Sayeed Syed3,Das Pratyush K.2ORCID,Kivioja Teemu2ORCID,Dave Kashyap1ORCID,Zhong Fan1,Nitta Kazuhiro R.1ORCID,Taipale Minna1ORCID,Popov Alexander4ORCID,Ginno Paul A.5,Domcke Silvia56,Yan Jian1ORCID,Schübeler Dirk56,Vinson Charles3ORCID,Taipale Jussi12ORCID

Affiliation:

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.

Abstract

Positives and negatives of methylated CpG When the DNA bases cytosine and guanine are next to each other, a methyl group is generally added to the pyrimidine, generating a mCpG dinucleotide. This modification alters DNA structure but can also affect function by inhibiting transcription factor (TF) binding. Yin et al. systematically analyzed the effect of CpG methylation on the binding of 542 human TFs (see the Perspective by Hughes and Lambert). In addition to inhibiting binding of some TFs, they found that mCpGs can promote binding of others, particularly TFs involved in development, such as homeodomain proteins. Science , this issue p. eaaj2239 ; see also p. 489

Funder

Academy of Finland Center of Excellence in Cancer Genetics

European Research Area SynBio

Center for Innovative Medicine at Karolinska Institutet

Knut and Alice Wallenberg Foundation

Göran Gustafsson Foundation

Vetenskapsrådet

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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