title: D4Z4 as a prototype of CTCF and lamins-dependent insulator in human cells.
abstract: Using cellular models that mimic the organizations of the subtelomeric 4q35 locus found in patients affected with Facio-Scapulo-Humeral Dystrophy (FSHD) and in healthy individuals, we recently investigated the biological function of the D4Z4 macrosatellite in this subtelomeric context.We demonstrated that D4Z4 acts as a CTCF and A-type lamins dependent insulator element exhibiting both enhancer- blocking and barrier activities, and displaces a telomere towards the nuclear periphery. This peripheral positioning activity lies within a short sequence that interacts with CTCF and A-type lamins. Depletion in either of these two proteins suppresses these perinuclear activities, revealing the existence of a subtelomeric sequence that is sufficient to position an adjacent telomere to the nuclear periphery. We discuss here the biological implications of these results in the light of our current knowledge in related fields and the potential implication of other CTCF and A-type lamins insulators in the light of human pathologies.
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, UCBL1, Lyon, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ottaviani
authors.forename: Caroline
authors.initials: C
authors.lastname: Schluth-Bolard
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.forename: Frédérique
authors.initials: F
authors.lastname: Magdinier
mesh_terms: D000076246:CCCTC-Binding Factor; D002467:Cell Nucleus / Q000378:metabolism; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D038101:Insulator Elements / Q000235:genetics*; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins