Purification, sequence, and cellular localization of a novel chromosomal protein that binds to Methylated DNA
Abstract
Methylation of mammalian DNA can lead to repression of transcription and alteration of chromatin structure. Recent evidence suggests that both effects are the result of an interaction between the methylated sites and methyl-CpG-binding proteins (MeCPs). MeCP1 has previously been detected in crude nuclear extracts. Here we report the identification, purification, and cDNA cloning of a novel MeCP called MeCP2. Unlike MeCP1, the new protein is able to bind to DNA that contains a single methyl-CpG pair. By staining with an antibody, we show that the distribution of MeCP2 along the chromosomes parallels that of methyl-CpG. In mouse, for example, MeCP2 is concentrated in pericentromeric heterochromatin, which contains a large fraction (about 40%) of all genomic 5-methylcytosine.
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MeCP2 is an abundant nuclear protein that is ubiquitously expressed throughout all human tissues, but is particularly abundant within neurons.
“MeCP2 is an abundant nuclear protein that was originally identified in a screen for proteins with methyl-DNA-specific binding activity. It is ubiquitously expressed throughout all human tissues, but is particularly abundant within neurons [52,53].”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [53]
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Self-citation
- Authors
- Lewis, J. D., Meehan, R. R., Henzel, W. J., Maurer-Fogy, I., Jeppesen, P., Klein, F., & Bird, A.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Genentech (US)
- Western General Hospital (GB)
- University of Vienna (AT)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1992-06
- Volume
- 69
- Issue
- 6
- Pages
- 905-914
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1975791071
- Cited by
- 1,371
- References
- 2
- Citations by year
- 2026: 27 · 2025: 31 · 2024: 33 · 2023: 31 · 2022: 39 · 2021: 48 · 2020: 36 · 2019: 45 · 2018: 51 · 2017: 47 · 2016: 56 · 2015: 38 · 2014: 57 · 2013: 74 · 2012: 42
- FWCI
- 10.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- 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
- MeCP2, methyl-CpG binding proteins, DNA methylation, chromatin structure, transcriptional repression, pericentromeric heterochromatin, 5-methylcytosine, protein purification, cDNA cloning, protein localization
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Chromosomal Proteins, Non-Histone, Cloning, Molecular, DNA, DNA-Binding Proteins, DNA, Satellite, Fluorescent Antibody Technique, Methylation, Molecular Sequence Data, Molecular Weight, Rats
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