Histone deacetylase-independent transcriptional repression by methyl-CpG-binding protein 2.
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.
Yu
F
F
Institut für Medizinische Biochemie und Molekularbiologie, Universitäts-Krankenhaus Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Thiesen
J
J
Strätling
W H
WH
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005982:Glutathione Transferase / Q000235:genetics; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007668:Kidney; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; C497392:MECP2 protein, human; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C012589:trichostatin A; D005982:Glutathione Transferase; C110550:HDAC1 protein, human; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases