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On how mammalian transcription factors recognize methylated DNA

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Pages 131-137 | Received 05 Dec 2012, Accepted 15 Jan 2013, Published online: 16 Jan 2013
 

Abstract

DNA methylation is an epigenetic mark that is essential for the development of mammals; it is frequently altered in diseases ranging from cancer to psychiatric disorders. The presence of DNA methylation attracts specialized methyl-DNA binding factors that can then recruit chromatin modifiers. These methyl-CpG binding proteins (MBPs) have key biological roles and can be classified into three structural families: methyl-CpG binding domain (MBD), zinc finger, and SET and RING finger-associated (SRA) domain. The structures of MBD and SRA proteins bound to methylated DNA have been previously determined and shown to exhibit two very different modes of methylated DNA recognition. The last piece of the puzzle has been recently revealed by the structural resolution of two different zinc finger proteins, Kaiso and ZFP57, in complex with methylated DNA. These structures show that the two methyl-CpG binding zinc finger proteins adopt differential methyl-CpG binding modes. Nonetheless, there are similarities with the MBD proteins suggesting some commonalities in methyl-CpG recognition across the various MBP domains. These fresh insights have consequences for the analysis of the many other zinc finger proteins present in the genome, and for the biology of methyl-CpG binding zinc finger proteins.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

P.A.D. thanks Benoit Miotto for suggesting the idea of this manuscript. Research in the lab of P.A.D. is supported by Fondation ARC, Institut National du Cancer, by grant ANR-11-LABX-0071 under program ANR-11-IDEX-0005-01 and Groupement des Entreprises Françaises pour la lutte contre le Cancer. BAB-K would like to thank the University of Utah Department of Chemistry for funding.