The methyl-CpG binding protein MeCP2 is essential for embryonic development in the mouse
Abstract
Vertebrate genomes are heavily methylated at cytosines in the sequence CpG. The biological role of this modification is probably mediated by DNA binding proteins that are either attracted to or repelled by methyl-CpG. MeCP2 is an abundant chromosomal protein that binds specifically to methylated DNA in vitro, and depends upon methyl-CpG for its chromosomal distribution in vivo. To assess the functional significance of MeCP2, the X-linked gene was mutated in male mouse embryonic stem (ES) cells using a promoterless gene-targeting construct containing a lacZ reporter gene. Mutant ES cells lacking MeCP2 grew with the same vigour as the parental line and were capable of considerable differentiation. Chimaeric embryos derived from several independent mutant lines, however, exhibited developmental defects whose severity was positively correlated with the contribution of mutant cells. The results demonstrate that MeCP2, like DNA methyltransferase, is dispensable in stem cells, but essential for embryonic development.
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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 [52]
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- Authors
- Tate, P., Skarnes, W., & Bird, A.
- Affiliations
- University of Edinburgh (GB)
- Biotechnology and Biological Sciences Research Council (GB)
- ORCID
- Bird, Adrian
- Venue
- Nature Genetics
- Published
- 1996-02
- Volume
- 12
- Issue
- 2
- Pages
- 205-208
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2088544665
- Cited by
- 231
- References
- 28
- Citations by year
- 2025: 3 · 2024: 3 · 2022: 7 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 10 · 2012: 10
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- MeCP2, methyl-CpG binding proteins, DNA methylation, CpG methylation, embryonic development, X-linked genes, embryonic stem cells, chimeric embryos, developmental defects, gene targeting, lacZ reporter, DNA methyltransferases
- MeSH terms
- Animals, beta-Galactosidase, Chimera, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Embryonic and Fetal Development, Genetic Linkage, Male, Recombinant Fusion Proteins, Repressor Proteins, RNA, Messenger, Stem Cells, X Chromosome, Gene Targeting, Mice, Methyl-CpG-Binding Protein 2
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