Abstract
Methyl-CpG-binding protein 2 (MeCP2) contains a transcriptional repression domain (TRD), which can act by recruitment of a large transcriptional co-repressor complex containing histone deacetylases HDAC1 and 2. We demonstrate here that transient transcription from the SV40 enhancer/promoter or the SV40 promoter is strongly repressed in a histone deacetylase-independent manner, since repression is not alleviated by Trichostatin A (TSA). In a mutational analysis, repression depends on a conserved 30 residue sequence containing two clusters of basic amino acids. Mutation of the first of these clusters inhibits in vitro interaction between TRD and mSin3A. Furthermore, a subdomain of the TRD containing the conserved 30-residue sequence and 16 flanking amino acids was sufficient to compromise VP16-activated transcription. In summary, our results indicate an alternative, histone deacetylase-independent pathway of transcriptional repression by MeCP2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Cell Line
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Chromosomal Proteins, Non-Histone*
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Conserved Sequence
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Enhancer Elements, Genetic
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Glutathione Transferase / genetics
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases / metabolism
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Humans
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Hydroxamic Acids / pharmacology
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Kidney
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Methyl-CpG-Binding Protein 2
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Mice
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Mutagenesis, Site-Directed
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Promoter Regions, Genetic*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / metabolism
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Simian virus 40 / genetics*
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Transcription, Genetic* / drug effects
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Transfection
Substances
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Hydroxamic Acids
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MECP2 protein, human
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Mecp2 protein, mouse
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Methyl-CpG-Binding Protein 2
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Recombinant Fusion Proteins
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Repressor Proteins
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trichostatin A
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Glutathione Transferase
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HDAC1 protein, human
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Hdac2 protein, mouse
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases