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  • The EMBO Journal (2009) 28, 2428 - 2436
  • doi:10.1038/emboj.2009.201

Published online: 30 July 2009

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

Alexandre Ottaviani1,4, Caroline Schluth-Bolard1, Sylvie Rival-Gervier1,2, Amina Boussouar1, Delphine Rondier1, Andrea M Foerster1,5, Julia Morere1, Serge Bauwens1, Sophie Gazzo3, Evelyne Callet-Bauchu3, Eric Gilson1 and Frédérique Magdinier1

  1. Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS UMR 5239, UCBL1, Lyon Cedex, France
  2. INRA, ENVA, UMR 1198, Biologie du développement et de la Reproduction, CNRS FRE 2857, Jouy-en-Josas, France
  3. Service d'Hématologie Biologique, Centre Hospitalier Lyon Sud—Hospices Civils de Lyon et Université Claude Bernard Lyon I, EA, Pierre-Bénite, Cedex, France

Correspondence to:

Eric Gilson, Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS UMR 5239, UCBL1, IFR128, 46 allée d'Italie, 69364 Lyon Cedex 07, France. Tel.:+33 4 7272 8453; Fax:+33 4 7272 8080; E-mail: eric.gilson@ens-lyon.fr

Frédérique Magdinier, Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS UMR 5239, UCBL1, IFR128, 46 allée d'Italie, 69364 Lyon Cedex 07, France. Tel.:+33 4 7272 8663; E-mail: frederique.magdinier@ens-lyon.fr

4Present address: Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

5Present address: Gregor Mendel-Institute of Molecular Plant Biology, Dr Bohr-Gasse 3, 1030 Vienna, Austria

Received 23 January 2009; Accepted 23 June 2009

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:

    • CTCF,
    • D4Z4,
    • FSHD,
    • nuclear periphery,
    • telomere