Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome

Bioessays. 2005 Jul;27(7):676-80. doi: 10.1002/bies.20266.

Abstract

Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting almost exclusively girls. Although mutations in methyl-CpG-binding protein (MeCP2) are known to be associated with RTT, gene expression patterns are not significantly altered in MeCP2-deficient cells. A recent study1 identified MeCP2-mediated histone modification and formation of a higher-order chromatin loop structure specifically associated with silent chromatin at the Dlx5-Dlx6 locus in normal cells, and its absence thereof in RTT patients. This altered expression of Dlx5 through loss of silent chromatin loop formation provides a molecular mechanism underlying RTT and proposes a novel role for MeCP2 in chromatin organization and imprinting.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • CpG Islands
  • DNA-Binding Proteins / metabolism*
  • Genomic Imprinting*
  • Histones / chemistry
  • Histones / metabolism
  • Homeodomain Proteins / metabolism*
  • Humans
  • Methyl-CpG-Binding Protein 2
  • Models, Genetic
  • Repressor Proteins / metabolism*
  • Rett Syndrome / genetics*
  • Transcription Factors

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DLX5 protein, human
  • DNA-Binding Proteins
  • Histones
  • Homeodomain Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins
  • Transcription Factors