Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome.
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.
Bapat
Sharmila
S
National Centre for Cell Science, Ganeshkhind, Pune, India.
Galande
Sanjeev
S
D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018392:Genomic Imprinting; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2; D008957:Models, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D015518:Rett Syndrome / Q000235:genetics*; D014157:Transcription Factors
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C100596:DLX5 protein, human; D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors