Methylation-Dependent and -Independent Genomic Targeting Principles of the MBD Protein Family
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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.
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MBD family proteins tend to bind regions with high methylation density.
“MBD family proteins tend to bind to regions with a high methylation density (that is, high methylation level and high CpG density)76”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [76]
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- Authors
- Baubec, T., Ivánek, R., Lienert, F., & Schübeler, D.
- Affiliations
- Friedrich Miescher Institute (CH)
- University of Basel (CH)
- Corresponding author
- Schübeler, Dirk
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 153
- Issue
- 2
- Pages
- 480-492
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2030513330
- Cited by
- 365
- References
- 58
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 21 · 2023: 17 · 2022: 24 · 2021: 29 · 2020: 19 · 2019: 27 · 2018: 27 · 2017: 34 · 2016: 38 · 2015: 37 · 2014: 41 · 2013: 14
- FWCI
- 19.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- methyl-CpG binding domain proteins, MBD2, MBD3, NuRD complex, hydroxymethylation, protein-protein interaction
- MeSH terms
- Amino Acid Sequence, Animals, Biotin, Chromatin, DNA-Binding Proteins, Humans, Molecular Sequence Data, Mutation, Sequence Alignment, Protein Structure, Tertiary, CpG Islands, DNA Methylation, Mice, Methyl-CpG-Binding Protein 2, Embryonic Stem Cells, Genome-Wide Association Study
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