Histone deacetylase-independent transcriptional repression by methyl-CpG-binding protein 2

Nucleic Acids Res. 2000 May 15;28(10):2201-6. doi: 10.1093/nar/28.10.2201.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Line
  • Chromosomal Proteins, Non-Histone*
  • Conserved Sequence
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic
  • Glutathione Transferase / genetics
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / pharmacology
  • Kidney
  • Methyl-CpG-Binding Protein 2
  • Mice
  • Mutagenesis, Site-Directed
  • Promoter Regions, Genetic*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / metabolism
  • Simian virus 40 / genetics*
  • Transcription, Genetic* / drug effects
  • Transfection

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Hydroxamic Acids
  • MECP2 protein, human
  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • trichostatin A
  • Glutathione Transferase
  • HDAC1 protein, human
  • Hdac2 protein, mouse
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylases