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CpG deamination creates transcription factor-binding sites with high efficiency

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons50662

Zemojtel,  T.
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50380

Kielbasa,  S. M.
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50074

Arndt,  P. F.
Evolutionary Genomics (Peter Arndt), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50091

Behrens,  S.
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50613

Vingron,  M.
Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Zemojtel, T., Kielbasa, S. M., Arndt, P. F., Behrens, S., Bourque, G., & Vingron, M. (2011). CpG deamination creates transcription factor-binding sites with high efficiency. Genome Biol Evol, 3, 1304-11. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22016335 http://gbe.oxfordjournals.org/content/3/1304.full.pdf.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-790E-A
Abstract
The formation of new transcription factor-binding sites (TFBSs) has a major impact on the evolution of gene regulatory networks. Clearly, single nucleotide mutations arising within genomic DNA can lead to the creation of TFBSs. Are molecular processes inducing single nucleotide mutations contributing equally to the creation of TFBSs? In the human genome, a spontaneous deamination of methylated cytosine in the context of CpG dinucleotides results in the creation of thymine (C --> T), and this mutation has the highest rate among all base substitutions. CpG deamination has been ascribed a role in silencing of transposons and induction of variation in regional methylation. We have previously shown that CpG deamination created thousands of p53-binding sites within genomic sequences of Alu transposons. Interestingly, we have defined a approximately 30 bp region in Alu sequence, which, depending on a pattern of CpG deamination, can be converted to functional p53-, PAX-6-, and Myc-binding sites. Here, we have studied single nucleotide mutational events leading to creation of TFBSs in promoters of human genes and in genomic regions bound by such key transcription factors as Oct4, NANOG, and c-Myc. We document that CpG deamination events can create TFBSs with much higher efficiency than other types of mutational events. Our findings add a new role to CpG methylation: We propose that deamination of methylated CpGs constitutes one of the evolutionary forces acting on mutational trajectories of TFBSs formation contributing to variability in gene regulation.