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Nucleic Acids Res
2000 Nov 01;2821:4172-9. doi: 10.1093/nar/28.21.4172.
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Functional consequences of Rett syndrome mutations on human MeCP2.
Yusufzai TM
,
Wolffe AP
.
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The neurodevelopmental disorder known as Rett syndrome has recently been linked to the methyl-CpG-binding transcriptional repressor, MeCP2. In this report we examine the consequences of these mutations on the function of MeCP2. The ability to bind specifically to methylated DNA and the transcription repression capabilities are tested, as well as the stability of proteins in vivo. We find that all missense mutations (R106W, R133C, F155S, T158M) within the methyl-binding domain impair selectivity for methylated DNA, and that all nonsense mutations (L138X, R168X, E235X, R255X, R270X, V288X, R294X) that truncate all or some of the transcriptional repression domain (TRD) affect the ability to repress transcription and have decreased levels of stability in vivo. Two missense mutations, one in the TRD (R306C) and one in the C-terminus (E397K), had no noticeable effects on MeCP2 function. Together, these results provide evidence of how Rett syndrome mutations can affect distinct functions of MeCP2 and give insight into these mutations that may contribute to the disease.
Almouzni,
Replication-coupled chromatin assembly is required for the repression of basal transcription in vivo.
1993, Pubmed,
Xenbase
Almouzni,
Replication-coupled chromatin assembly is required for the repression of basal transcription in vivo.
1993,
Pubmed
,
Xenbase
Amir,
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
1999,
Pubmed
Ballestar,
Effects of Rett syndrome mutations of the methyl-CpG binding domain of the transcriptional repressor MeCP2 on selectivity for association with methylated DNA.
2000,
Pubmed
Bellini,
Coilin shuttles between the nucleus and cytoplasm in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Bird,
Transcriptional noise and the evolution of gene number.
1995,
Pubmed
Buschhausen,
Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene.
1987,
Pubmed
Chandler,
The methyl-CpG binding transcriptional repressor MeCP2 stably associates with nucleosomal DNA.
1999,
Pubmed
,
Xenbase
Cheadle,
Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location.
2000,
Pubmed
Coy,
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 expression.
1999,
Pubmed
De Bona,
Preserved speech variant is allelic of classic Rett syndrome.
2000,
Pubmed
Hendrich,
Identification and characterization of a family of mammalian methyl-CpG binding proteins.
1998,
Pubmed
Huppke,
Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients.
2000,
Pubmed
Jones,
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription.
1998,
Pubmed
,
Xenbase
Kaludov,
MeCP2 driven transcriptional repression in vitro: selectivity for methylated DNA, action at a distance and contacts with the basal transcription machinery.
2000,
Pubmed
Kass,
DNA methylation directs a time-dependent repression of transcription initiation.
1997,
Pubmed
,
Xenbase
Lewis,
Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA.
1992,
Pubmed
Meehan,
Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA.
1992,
Pubmed
Nan,
Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2.
1993,
Pubmed
Nan,
Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex.
1998,
Pubmed
Ohki,
Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1.
1999,
Pubmed
Razin,
CpG methylation, chromatin structure and gene silencing-a three-way connection.
1998,
Pubmed
Tate,
The methyl-CpG binding protein MeCP2 is essential for embryonic development in the mouse.
1996,
Pubmed
Van den Veyver,
Methyl-CpG-binding protein 2 mutations in Rett syndrome.
2000,
Pubmed
Wakefield,
The solution structure of the domain from MeCP2 that binds to methylated DNA.
1999,
Pubmed
Wan,
Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots.
1999,
Pubmed
Xiang,
Mutation screening in Rett syndrome patients.
2000,
Pubmed
Yoder,
Cytosine methylation and the ecology of intragenomic parasites.
1997,
Pubmed
Yu,
Histone deacetylase-independent transcriptional repression by methyl-CpG-binding protein 2.
2000,
Pubmed
