ArticleBiochemistry2014
Unusual characteristics of the DNA binding domain of epigenetic regulatory protein MeCP2 determine its binding specificity.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- MeCP2 MBD-ID module: a unified DNA/RNA binding interface disrupted in Rett syndrome.Nucleic acids research · 2026Article
- DNA methylation, nucleic acid structure, and rett mutations tune MeCP2 binding affinity and cooperativity.The Journal of biological chemistry · 2026Article
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- Exploring the complexity of MECP2 function in Rett syndrome.Nature reviews. Neuroscience · 2025Review
- Biochemical and cellular insights into the Baz2B protein, a non-catalytic subunit of the chromatin remodeling complex.Nucleic acids research · 2024Article
- Epigenetics in rare neurological diseases.Frontiers in cell and developmental biology · 2024Review
- Dose-Dependent Nuclear Delivery and Transcriptional Repression with a Cell-Penetrant MeCP2.ACS central science · 2023Article
- Review
- DNA looping by two 5-methylcytosine-binding proteins quantified using nanofluidic devices.Epigenetics & chromatin · 2020Article
- Identification of Novel MeCP2 Cancer-Associated Target Genes and Post-Translational Modifications.Frontiers in oncology · 2020Article
- Global DNA Methylation Patterns in Human Gliomas and Their Interplay with Other Epigenetic Modifications.International journal of molecular sciences · 2019Review
- The C-terminal D/E-rich domain of MBD3 is a putative Z-DNA mimic that competes for Zα DNA-binding activity.Nucleic acids research · 2018Article
- Reading cytosine modifications within chromatin.Transcription · 2018Review
- DNA Methylation and Adult Neurogenesis.Brain plasticity (Amsterdam, Netherlands) · 2017Review
- Review
- Impact of cytosine methylation on DNA binding specificities of human transcription factors.Science (New York, N.Y.) · 2017Article
- MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain.PLoS genetics · 2017Article
- Binding of MBD proteins to DNA blocks Tet1 function thereby modulating transcriptional noise.Nucleic acids research · 2017Article
- The intervening domain from MeCP2 enhances the DNA affinity of the methyl binding domain and provides an independent DNA interaction site.Scientific reports · 2017Article
- Binding Analysis of Methyl-CpG Binding Domain of MeCP2 and Rett Syndrome Mutations.ACS chemical biology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The protein MeCP2 mediates epigenetic regulation by binding methyl-CpG (mCpG) sites on chromatin. MeCP2 consists of six domains of which one, the methyl binding domain (MBD), binds mCpG sites in duplex DNA. We show that solution conditions with physiological or greater salt concentrations or the presence of nonspecific competitor DNA is necessary for the MBD to discriminate mCpG from CpG with high specificity. The specificity for mCpG over CpG is >100-fold under these solution conditions. In contrast, the MBD does not discriminate hydroxymethyl-CpG from CpG. The MBD is unusual among site-specific DNA binding proteins in that (i) specificity is not conferred by the enhanced affinity for the specific site but rather by suppression of its affinity for generic DNA, (ii) its specific binding to mCpG is highly electrostatic, and (iii) it takes up as well as displaces monovalent cations upon DNA binding. The MBD displays an unusually high affinity for single-stranded DNA independent of modification or sequence. In addition, the MBD forms a discrete dimer on DNA via a noncooperative binding pathway. Because the affinity of the second monomer is 1 order of magnitude greater than that of nonspecific binding, the MBD dimer is a unique molecular complex. The significance of these results in the context of neuronal function and development and MeCP2-related developmental disorders such as Rett syndrome is discussed.
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