Identification of a perinuclear positioning element in human subtelomeres that requires A-type lamins and CTCF

Alexandre Ottaviani 1 Caroline Schluth-Bolard 1 Sylvie Rival-Gervier 2 Amina Boussouar 1 Delphine Rondier Andrea Foerster Julia Morere 3 Serge Bauwens 4 Sophie Gazzo 1 Evelyne Callet-Bauchu 5 Eric Gilson 1 Frédérique Magdinier 6, 3
1 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
2 BDR - Biologie du Développement et Reproduction
3 GMGF - Génétique Médicale et Génomique Fonctionnelle
4 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
5 Laboratoire d'Hématologie
6 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
Abstract : The localization of genes within the nuclear space is of paramount importance for proper genome functions. However, very little is known on the cis-acting elements determining subnuclear positioning of chromosome segments. We show here that the D4Z4 human subtelomeric repeat localizes a telomere at the nuclear periphery. This perinuclear activity lies within an 80 bp sequence included within a region known to interact with CTCF and A-type Lamins. We further show that a reduced level of either CTCF or A-type Lamins suppresses the perinuclear activities of D4Z4 and that an array of multimerized D4Z4 sequence, which has lost its ability to bind CTCF and A-type Lamins, is not localized at the periphery. Overall, these findings reveal the existence of an 80 bp D4Z4 sequence that is sufficient to position an adjacent telomere to the nuclear periphery in a CTCF and A-type lamins-dependent manner. Strikingly, this sequence includes a 30 bp GA-rich motif, which binds CTCF and is present at several locations in the human genome.
Keywords : telomere CTCF genome stability & dynamics D4Z4 FSHD nuclear periphery
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Alexandre Ottaviani, Caroline Schluth-Bolard, Sylvie Rival-Gervier, Amina Boussouar, Delphine Rondier, et al.. Identification of a perinuclear positioning element in human subtelomeres that requires A-type lamins and CTCF. EMBO Journal, EMBO Press, 2009, 28, pp.2428 - 2436. ⟨hal-01663788⟩

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