Identification of a perinuclear positioning element in human subtelomeres that requires A-type lamins and CTCF.
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.
Ottaviani
Alexandre
A
Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS UMR 5239, UCBL1, Lyon Cedex, France.
Schluth-Bolard
Caroline
C
Rival-Gervier
Sylvie
S
Boussouar
Amina
A
Rondier
Delphine
D
Foerster
Andrea M
AM
Morere
Julia
J
Bauwens
Serge
S
Gazzo
Sophie
S
Callet-Bauchu
Evelyne
E
Gilson
Eric
E
Magdinier
Frédérique
F
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D000076246:CCCTC-Binding Factor; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D038101:Insulator Elements; D034904:Lamin Type A / Q000378:metabolism*; D019901:Locus Control Region; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D034904:Lamin Type A; D012097:Repressor Proteins