title: On how mammalian transcription factors recognize methylated DNA.
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.
authors: Department of Chemistry, University of Utah, Salt Lake City, UT, USA. koehntop@chem.utah.edu
authors: Bethany A
authors: BA
authors: Buck-Koehntop
authors: Pierre-Antoine
authors: PA
authors: Defossez
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000235:genetics* / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C454113:Slc39a6 protein, mouse; D014157:Transcription Factors; C492254:ZBTB33 protein, human
keywords: DNA methylation; Kaiso; MBD; SRA domain; ZFP57; methyl-CpG binding proteins; protein structure; zinc finger