Methylation-dependent and -independent genomic targeting principles of the MBD protein family.
- Baubec T Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
- Ivánek R
- Lienert F
- Schübeler D
- 2013-04-16
Published in:
- Cell. - 2013
Amino Acid Sequence
Animals
Biotin
Chromatin
CpG Islands
DNA Methylation
DNA-Binding Proteins
Embryonic Stem Cells
Genome-Wide Association Study
Humans
Methyl-CpG-Binding Protein 2
Mice
Molecular Sequence Data
Mutation
Protein Structure, Tertiary
Sequence Alignment
English
To gain insight into the cellular readout of DNA methylation, we established a strategy for systematically profiling the genome-wide distribution of chromatin-interacting factors. This enabled us to create genomic maps for the methyl-CpG-binding domain (MBD) family of proteins, including disease-relevant mutants, deletions, and isoforms. In vivo binding of MBD proteins occurs predominantly as a linear function of local methylation density, requiring functional MBD domains and methyl-CPGs. This interaction directs specificity of MBD proteins to methylated, CpG-dense, and inactive regulatory regions. In contrast, binding to unmethylated sites varies between MBD proteins and is mediated via alternative domains or protein-protein interactions. Such targeting is exemplified by NuRD-complex-mediated tethering of MBD2 to a subset of unmethylated, active regulatory regions. Interestingly, MBD3 also occupies these sites, but like MBD2, binding is independent of the presence of hydroxymethylation. These functional binding maps reveal methylation-dependent and -independent binding modes and revise current models of DNA methylation readout through MBD proteins.
- Language
-
- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1016/j.cell.2013.03.011
- PMID 23582333
- Persistent URL
- https://sonar.ch/global/documents/202098
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