Identification of a Perinuclear Positioning Element in Human Subtelomeres That Requires A-type Lamins and CTCF

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2009 Aug 1

PMID 19644448

Citations 45

Authors

Alexandre Ottaviani

Caroline Schluth-Bolard

Sylvie Rival-Gervier

Amina Boussouar

Delphine Rondier

Andrea M Foerster

Julia Morere

Serge Bauwens

Sophie Gazzo

Evelyne Callet-Bauchu

Eric Gilson

Frederique Magdinier

Affiliations

Soon will be listed here.

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.

Citing Articles

Multifaceted role of CTCF in X-chromosome inactivation.

Bammidi L, Gayen S Chromosoma. 2024; 133(4):217-231.

PMID: 39433641 DOI: 10.1007/s00412-024-00826-w.

Complex 4q35 and 10q26 Rearrangements: A Challenge for Molecular Diagnosis of Patients With Facioscapulohumeral Dystrophy.

Delourme M, Charlene C, Gerard L, Ganne B, Perrin P, Vovan C Neurol Genet. 2023; 9(3):e200076.

PMID: 37200893 PMC: 10188231. DOI: 10.1212/NXG.0000000000200076.

Close Ties between the Nuclear Envelope and Mammalian Telomeres: Give Me Shelter.

Pennarun G, Picotto J, Bertrand P Genes (Basel). 2023; 14(4).

PMID: 37107534 PMC: 10137478. DOI: 10.3390/genes14040775.

Progerin impairs 3D genome organization and induces fragile telomeres by limiting the dNTP pools.

Kychygina A, DallOsto M, Allen J, Cadoret J, Piras V, Pickett H Sci Rep. 2021; 11(1):13195.

PMID: 34162976 PMC: 8222272. DOI: 10.1038/s41598-021-92631-z.

Subtelomeric Transcription and its Regulation.

Kwapisz M, Morillon A J Mol Biol. 2020; 432(15):4199-4219.

PMID: 32035903 PMC: 7374410. DOI: 10.1016/j.jmb.2020.01.026.

References

Gonzalez-Suarez I, Redwood A, Perkins S, Vermolen B, Lichtensztejin D, Grotsky D . Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J. 2009; 28(16):2414-27. PMC: 2735177. DOI: 10.1038/emboj.2009.196. View

Taddei A, Van Houwe G, Hediger F, Kalck V, Cubizolles F, Schober H . Nuclear pore association confers optimal expression levels for an inducible yeast gene. Nature. 2006; 441(7094):774-8. DOI: 10.1038/nature04845. View

Fourel G, Revardel E, Koering C, Gilson E . Cohabitation of insulators and silencing elements in yeast subtelomeric regions. EMBO J. 1999; 18(9):2522-37. PMC: 1171334. DOI: 10.1093/emboj/18.9.2522. View

Guelen L, Pagie L, Brasset E, Meuleman W, Faza M, Talhout W . Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature. 2008; 453(7197):948-51. DOI: 10.1038/nature06947. View

Kumaran R, Spector D . A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol. 2008; 180(1):51-65. PMC: 2213611. DOI: 10.1083/jcb.200706060. View

Maillet L, Boscheron C, Gotta M, Marcand S, Gilson E, Gasser S . Evidence for silencing compartments within the yeast nucleus: a role for telomere proximity and Sir protein concentration in silencer-mediated repression. Genes Dev. 1996; 10(14):1796-811. DOI: 10.1101/gad.10.14.1796. View

Wendt K, Yoshida K, Itoh T, Bando M, Koch B, Schirghuber E . Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature. 2008; 451(7180):796-801. DOI: 10.1038/nature06634. View

Gabellini D, Green M, Tupler R . Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Cell. 2002; 110(3):339-48. DOI: 10.1016/s0092-8674(02)00826-7. View

Kumaran R, Muralikrishna B, Parnaik V . Lamin A/C speckles mediate spatial organization of splicing factor compartments and RNA polymerase II transcription. J Cell Biol. 2002; 159(5):783-93. PMC: 2173379. DOI: 10.1083/jcb.200204149. View

10.

Andrulis E, Neiman A, Zappulla D, Sternglanz R . Perinuclear localization of chromatin facilitates transcriptional silencing. Nature. 1998; 394(6693):592-5. DOI: 10.1038/29100. View

11.

Tam R, Smith K, Lawrence J . The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres. J Cell Biol. 2004; 167(2):269-79. PMC: 2172553. DOI: 10.1083/jcb.200403128. View

12.

Gilson E, Laroche T, Gasser S . Telomeres and the functional architecture of the nucleus. Trends Cell Biol. 1993; 3(4):128-34. DOI: 10.1016/0962-8924(93)90175-z. View

13.

Parelho V, Hadjur S, Spivakov M, Leleu M, Sauer S, Gregson H . Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell. 2008; 132(3):422-33. DOI: 10.1016/j.cell.2008.01.011. View

14.

Yusufzai T, Tagami H, Nakatani Y, Felsenfeld G . CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell. 2004; 13(2):291-8. DOI: 10.1016/s1097-2765(04)00029-2. View

15.

van Overveld P, Enthoven L, Ricci E, Rossi M, Felicetti L, Jeanpierre M . Variable hypomethylation of D4Z4 in facioscapulohumeral muscular dystrophy. Ann Neurol. 2005; 58(4):569-76. DOI: 10.1002/ana.20625. View

16.

Petrov A, Allinne J, Pirozhkova I, Laoudj D, Lipinski M, Vassetzky Y . A nuclear matrix attachment site in the 4q35 locus has an enhancer-blocking activity in vivo: implications for the facio-scapulo-humeral dystrophy. Genome Res. 2007; 18(1):39-45. PMC: 2134777. DOI: 10.1101/gr.6620908. View

17.

Rawlins D, Shaw P . Localization of ribosomal and telomeric DNA sequences in intact plant nuclei by in-situ hybridization and three-dimensional optical microscopy. J Microsc. 1990; 157(Pt 1):83-9. DOI: 10.1111/j.1365-2818.1990.tb02949.x. View

18.

Koering C, Pollice A, Zibella M, Bauwens S, Puisieux A, Brunori M . Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO Rep. 2002; 3(11):1055-61. PMC: 1307600. DOI: 10.1093/embo-reports/kvf215. View

19.

Freitas-Junior L, Bottius E, Pirrit L, Deitsch K, Scheidig C, Guinet F . Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature. 2000; 407(6807):1018-22. DOI: 10.1038/35039531. View

20.

Nagai S, Dubrana K, Tsai-Pflugfelder M, Davidson M, Roberts T, Brown G . Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science. 2008; 322(5901):597-602. PMC: 3518492. DOI: 10.1126/science.1162790. View