The major form of MeCP2 has a novel N-terminus generated by alternative splicing
- 8 March 2004
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 32 (5) , 1818-1823
- https://doi.org/10.1093/nar/gkh349
Abstract
MeCP2 is a methyl-CpG binding protein that can repress transcription of nearby genes. In humans, mutations in the MECP2 gene are the major cause of Rett syndrome. By searching expressed sequence tag (EST) databases we have found a novel MeCP2 splice isoform (MeCP2alpha) which encodes a distinct N-terminus. We demonstrate that the MeCP2alpha mRNA splice variant is more abundant than the previously annotated MeCP2 mRNA (MeCP2beta) in mouse tissues and human brain. Furthermore, MeCP2beta mRNA has an upstream open reading frame that inhibits its translation. As a result of these differences, >90% of MeCP2 in mouse brain is MeCP2alpha. Both protein isoforms are nuclear and colocalize with densely methylated heterochromatic foci in mouse cells. The presence of a previously unknown MeCP2 isoform has implications for the genetic screening of Rett syndrome patients and for studies of the functional significance of MeCP2.Keywords
This publication has 33 references indexed in Scilit:
- Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2Science, 2003
- DNA methylation and Rett syndromeHuman Molecular Genetics, 2003
- RETRACTED: A Mutant Form of MeCP2 Protein Associated with Human Rett Syndrome Cannot Be Displaced from Methylated DNA by Notch in Xenopus EmbryosMolecular Cell, 2003
- The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone MethylationJournal of Biological Chemistry, 2003
- Clinical manifestations and stages of rett syndromeMental Retardation and Developmental Disabilities Research Reviews, 2002
- Analysis of Chromatin-Immunopurified MeCP2-Associated FragmentsBiochemical and Biophysical Research Communications, 2001
- Methylation-Mediated Proviral Silencing Is Associated with MeCP2 Recruitment and Localized Histone H3 DeacetylationMolecular and Cellular Biology, 2001
- A complex pattern of evolutionary conservation and alternative polyadenylation within the long 3"-untranslated region of the methyl-CpG-binding protein 2 gene (MeCP2) suggests a regulatory role in gene expressionHuman Molecular Genetics, 1999
- Genetic and Physical Mapping of a Gene Encoding a Methyl CpG Binding Protein, Mecp2, to the Mouse X ChromosomeGenomics, 1994
- Purification, sequence, and cellular localization of a novel chromosomal protein that binds to Methylated DNACell, 1992