1. A nuclear matrix attachment site in the 4q35 locus has an enhancer-blocking activity in vivo: Implications for the facio-scapulo-humeral dystrophy
- Author
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Jeanne Allinne, Marc Lipinski, Iryna Pirozhkova, Andrei Petrov, Dalila Laoudj, Yegor S. Vassetzky, Interactions moléculaires et cancer (IMC (UMR 8126)), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Muscles et pathologies, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), and MORNET, Dominique
- Subjects
musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,Letter ,Transcription, Genetic ,[SDV]Life Sciences [q-bio] ,Quantitative Trait Loci ,Enhancer RNAs ,Biology ,Myoblasts ,Transcription (biology) ,Genetics ,medicine ,Humans ,Nuclear protein ,Muscular dystrophy ,Scaffold/matrix attachment region ,Enhancer ,Genetics (clinical) ,Models, Genetic ,Microfilament Proteins ,Nuclear Proteins ,Proteins ,RNA-Binding Proteins ,Dystrophy ,Matrix Attachment Regions ,Nuclear matrix ,medicine.disease ,Molecular biology ,Muscular Dystrophy, Facioscapulohumeral ,Up-Regulation ,[SDV] Life Sciences [q-bio] ,Enhancer Elements, Genetic ,Chromosomes, Human, Pair 4 ,HeLa Cells - Abstract
Facio-scapulo-humeral dystrophy (FSHD), a muscular hereditary disease with a prevalence of 1 in 20,000, is caused by a partial deletion of a subtelomeric repeat array on chromosome 4q. Earlier, we demonstrated the existence in the vicinity of the D4Z4 repeat of a nuclear matrix attachment site, FR-MAR, efficient in normal human myoblasts and nonmuscular human cells but much weaker in muscle cells from FSHD patients. We now report that the D4Z4 repeat contains an exceptionally strong transcriptional enhancer at its 5′-end. This enhancer up-regulates transcription from the promoter of the neighboring FRG1 gene. However, an enhancer blocking activity was found present in FR-MAR that in vitro could protect transcription from the enhancer activity of the D4Z4 array. In vivo, transcription from the FRG1 and FRG2 genes could be down- or up-regulated depending on whether or not FR-MAR is associated with the nuclear matrix. We propose a model for an etiological role of the delocalization of FR-MAR in the genesis of FSHD.
- Published
- 2007