E. Gilson and F. Magdinier, We thank Dr Gary Felsenfeld for the kind gift of the pNI, pJC5-4 and pJC3-4 vectors and discussion. We acknowledge the facilities of the IFR 128 for Flow Cytometry We are grateful to Nicolas Lévy, Gisèle Bonne, Evani-Viegas Pequignot, Rossella Tupler, the members of the FSHD consortium coordinated by the Association Française contre les Myopathies (AFM) and the members of the laboratory for helpful discussion Telomeric position effect: From the yeast paradigm to human pathologies, Biochimie, vol.90, pp.93-107, 2008.

C. Wijmenga, J. Hewitt, L. Sandkuijl, L. Clark, and T. Wright, Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy, Nature Genetics, vol.44, issue.1, pp.26-30, 1992.
DOI : 10.1111/j.1399-0004.1990.tb03614.x

S. Winokur, U. Bengtsson, J. Feddersen, K. Mathews, and B. Weiffenbach, The DNA rearrangement associated with facioscapulohumeral muscular dystrophy involves a heterochromatin-associated repetitive element: Implications for a role of chromatin structure in the pathogenesis of the disease, Chromosome Research, vol.14, issue.3, pp.225-234, 1994.
DOI : 10.1007/978-1-4684-0269-8

J. Van-deutekom, C. Wijmenga, E. Van-tienhoven, A. Gruter, and J. Hewitt, FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit, Human Molecular Genetics, vol.2, issue.12, pp.2037-2042, 1993.
DOI : 10.1093/hmg/2.12.2037

R. Tawil, D. Figlewicz, R. Griggs, and B. Weiffenbach, Facioscapulohumeral Dystrophy, Ann Neurol, vol.43, pp.279-282, 1998.
DOI : 10.1016/B978-0-12-410529-4.00097-8

URL : https://hal.archives-ouvertes.fr/hal-00811730

M. Dixit, E. Ansseau, A. Tassin, S. Winokur, and R. Shi, DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1, Proceedings of the National Academy of Sciences, vol.83, issue.3, pp.18157-18162, 2007.
DOI : 10.1007/s00109-004-0583-7

D. Gabellini, M. Green, and R. Tupler, Inappropriate Gene Activation in FSHD, Cell, vol.110, issue.3, pp.339-348, 2002.
DOI : 10.1016/S0092-8674(02)00826-7

URL : https://doi.org/10.1016/s0092-8674(02)00826-7

T. Rijkers, G. Deidda, S. Van-koningsbruggen, M. Van-geel, and R. Lemmers, FRG2, an FSHD candidate gene, is transcriptionally upregulated in differentiating primary myoblast cultures of FSHD patients, Journal of Medical Genetics, vol.41, issue.11, pp.826-836, 2004.
DOI : 10.1136/jmg.2004.019364

S. Van-der-maarel and R. Frants, The D4Z4 Repeat???Mediated Pathogenesis of Facioscapulohumeral Muscular Dystrophy, The American Journal of Human Genetics, vol.76, issue.3, pp.375-386, 2005.
DOI : 10.1086/428361

D. Gabellini, M. Green, and R. Tupler, When enough is enough: genetic diseases associated with transcriptional derepression, Current Opinion in Genetics & Development, vol.14, issue.3, pp.301-307, 2004.
DOI : 10.1016/j.gde.2004.04.010

J. Hewitt, R. Lyle, L. Clark, E. Valleley, and T. Wright, Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystropothhy, Human Molecular Genetics, vol.3, issue.8, pp.1287-1295, 1994.
DOI : 10.1093/hmg/3.8.1287

R. Lyle, T. Wright, L. Clark, and J. Hewitt, The FSHD-Associated Repeat, D4Z4, Is a Member of a Dispersed Family of Homeobox-Containing Repeats, Subsets of Which Are Clustered on the Short Arms of the Acrocentric Chromosomes, Genomics, vol.28, issue.3, pp.389-397, 1995.
DOI : 10.1006/geno.1995.1166

P. Masny, U. Bengtsson, S. Chung, J. Martin, and B. Van-engelen, Localization of 4q35.2 to the nuclear periphery: is FSHD a nuclear envelope disease?, Human Molecular Genetics, vol.13, issue.17, pp.1857-1871, 2004.
DOI : 10.1093/hmg/ddh205

R. Tam, K. Smith, and J. Lawrence, The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres, The Journal of Cell Biology, vol.114, issue.2, pp.269-279, 2004.
DOI : 10.1016/S1097-2765(04)00029-2

A. Petrov, I. Pirozhkova, G. Carnac, D. Laoudj, and M. Lipinski, Chromatin loop domain organization within the 4q35 locus in facioscapulohumeral dystrophy patients versus normal human myoblasts, Proceedings of the National Academy of Sciences, vol.19, issue.3, pp.6982-6987, 2006.
DOI : 10.1006/meth.1999.0875

J. Baur, Y. Zou, J. Shay, and W. Wright, Telomere Position Effect in Human Cells, Science, vol.292, issue.5524, pp.2075-2077, 2001.
DOI : 10.1126/science.1062329

C. Koering, A. Pollice, M. Zibella, S. Bauwens, and A. Puisieux, Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity, EMBO reports, vol.3, issue.11, pp.1055-1061, 2002.
DOI : 10.1093/embo-reports/kvf215

URL : https://hal.archives-ouvertes.fr/hal-01596225

A. West, M. Gaszner, and G. Felsenfeld, Insulators: many functions, many mechanisms, Genes & Development, vol.16, issue.3, pp.271-288, 2002.
DOI : 10.1101/gad.954702

URL : http://genesdev.cshlp.org/content/16/3/271.full.pdf

J. Chung, M. Whiteley, and G. Felsenfeld, A 5??? element of the chicken ??-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila, Cell, vol.74, issue.3, pp.505-514, 1993.
DOI : 10.1016/0092-8674(93)80052-G

M. Gaszner and G. Felsenfeld, Insulators: exploiting transcriptional and epigenetic mechanisms, Nature Reviews Genetics, vol.9, issue.9, pp.703-713, 2006.
DOI : 10.1128/MCB.16.6.2802

G. Filippova, Genetics and Epigenetics of the Multifunctional Protein CTCF, Curr Top Dev Biol, vol.80, pp.337-360, 2008.
DOI : 10.1016/S0070-2153(07)80009-3

A. Bell and G. Felsenfeld, Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene, Nature, vol.99, issue.6785, pp.482-485, 2000.
DOI : 10.1016/S0092-8674(00)81546-9

A. Bell, A. West, and G. Felsenfeld, The Protein CTCF Is Required for the Enhancer Blocking Activity of Vertebrate Insulators, Cell, vol.98, issue.3, pp.387-396, 1999.
DOI : 10.1016/S0092-8674(00)81967-4

F. Magdinier, T. Yusufzai, and G. Felsenfeld, Genes, Journal of Biological Chemistry, vol.15, issue.24, pp.25381-25389, 2004.
DOI : 10.1128/MCB.15.1.198

URL : https://hal.archives-ouvertes.fr/hal-00868855

K. Wendt, K. Yoshida, T. Itoh, M. Bando, and B. Koch, Cohesin mediates transcriptional insulation by CCCTC-binding factor, Nature, vol.119, issue.7180, pp.796-801, 2008.
DOI : 10.1038/nature06634

A. West, S. Huang, M. Gaszner, M. Litt, and G. Felsenfeld, Recruitment of Histone Modifications by USF Proteins at a Vertebrate Barrier Element, Molecular Cell, vol.16, issue.3, pp.453-463, 2004.
DOI : 10.1016/j.molcel.2004.10.005

F. Recillas-targa, M. Pikaart, B. Burgess-beusse, A. Bell, and M. Litt, Position-effect protection and enhancer blocking by the chicken ??-globin insulator are separable activities, Proceedings of the National Academy of Sciences, vol.7, issue.16, pp.6883-6888, 2002.
DOI : 10.1073/pnas.160159597

URL : http://www.pnas.org/content/99/10/6883.full.pdf

T. Gerasimova, K. Byrd, and V. Corces, A Chromatin Insulator Determines the Nuclear Localization of DNA, Molecular Cell, vol.6, issue.5, pp.1025-1035, 2000.
DOI : 10.1016/S1097-2765(00)00101-5

M. Capelson and V. Corces, Boundary elements and nuclear organization, Biology of the Cell, vol.96, issue.8, pp.617-629, 2004.
DOI : 10.1016/j.biolcel.2004.06.004

URL : http://onlinelibrary.wiley.com/doi/10.1016/j.biolcel.2004.06.004/pdf

T. Gerasimova, E. Lei, A. Bushey, and V. Corces, Coordinated Control of dCTCF and gypsy Chromatin Insulators in Drosophila, Molecular Cell, vol.28, issue.5, pp.761-772, 2007.
DOI : 10.1016/j.molcel.2007.09.024

T. Yusufzai, H. Tagami, Y. Nakatani, and G. Felsenfeld, CTCF Tethers an Insulator to Subnuclear Sites, Suggesting Shared Insulator Mechanisms across Species, Molecular Cell, vol.13, issue.2, pp.291-298, 2004.
DOI : 10.1016/S1097-2765(04)00029-2

URL : https://doi.org/10.1016/s1097-2765(04)00029-2

V. Parelho, S. Hadjur, M. Spivakov, M. Leleu, and S. Sauer, Cohesins Functionally Associate with CTCF on Mammalian Chromosome Arms, Cell, vol.132, issue.3, pp.422-433, 2008.
DOI : 10.1016/j.cell.2008.01.011

URL : https://doi.org/10.1016/j.cell.2008.01.011

L. Guelen, L. Pagie, E. Brasset, W. Meuleman, and M. Faza, Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions, Nature, 2008.

B. Chadwick, DXZ4 chromatin adopts an opposing conformation to that of the surrounding chromosome and acquires a novel inactive X-specific role involving CTCF and antisense transcripts, Genome Research, vol.18, issue.8, 2008.
DOI : 10.1101/gr.075713.107

P. Lunt, P. Jardine, M. Koch, J. Maynard, and M. Osborn, Correlation between fragment size at D4F104S1 and age at onset or at wheelchair use, with a possible generational effect, accounts for much phenotypic variation in 4q35-facioscapulohumeral muscular dystrophy (FSHD), Human Molecular Genetics, vol.4, issue.5, 1995.
DOI : 10.1093/hmg/4.5.951

R. Tawil, J. Forrester, R. Griggs, J. Mendell, and J. Kissel, Evidence for anticipation and association of deletion size with severity in facioscapulohumerd muscular dystrophy, Annals of Neurology, vol.36, issue.6, pp.744-748, 1996.
DOI : 10.1212/WNL.44.3_Part_1.442

R. Lemmers, P. De-kievit, L. Sandkuijl, G. Padberg, and G. Van-ommen, Facioscapulohumeral muscular dystrophy is uniquely associated with one of the two variants of the 4q subtelomere, Nature Genetics, vol.205, issue.2, pp.235-236, 2002.
DOI : 10.1038/ng0295-132

N. Thomas, K. Wiseman, G. Spurlock, M. Macdonald, and D. Ustek, A large patient study confirming that facioscapulohumeral muscular dystrophy (FSHD) disease expression is almost exclusively associated with an FSHD locus located on a 4qA-defined 4qter subtelomere, Journal of Medical Genetics, vol.44, issue.3, pp.215-218, 2007.
DOI : 10.1136/jmg.2006.042804

R. Meneveri, A. Agresti, D. Valle, G. Talarico, D. Siccardi et al., Identification of a human clustered G + C-rich DNA family of repeats (Sau3A family), Journal of Molecular Biology, vol.186, issue.3, pp.483-489, 1985.
DOI : 10.1016/0022-2836(85)90123-8

P. Van-overveld, L. Enthoven, E. Ricci, M. Rossi, and L. Felicetti, Variable hypomethylation of D4Z4 in facioscapulohumeral muscular dystrophy, Annals of Neurology, vol.39, issue.4, pp.569-576, 2005.
DOI : 10.1002/ana.20625

A. Hark, C. Schoenherr, D. Katz, R. Ingram, and J. Levorse, CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus, Nature, vol.20, issue.6785, pp.486-489, 2000.
DOI : 10.1093/nar/20.14.3555

G. Jiang, F. Yang, P. Van-overveld, V. Vedanarayanan, and S. Van-der-maarel, Testing the position-effect variegation hypothesis for facioscapulohumeral muscular dystrophy by analysis of histone modification and gene expression in subtelomeric 4q, Human Molecular Genetics, vol.12, issue.22, pp.2909-2921, 2003.
DOI : 10.1093/hmg/ddg323

K. Tsumagari, L. Qi, K. Jackson, C. Shao, and M. Lacey, Epigenetics of a tandem DNA repeat: chromatin DNaseI sensitivity and opposite methylation changes in cancers, Nucleic Acids Research, vol.36, issue.7, pp.2196-2207, 2008.
DOI : 10.1093/nar/gkn055

M. Bakay, Z. Wang, G. Melcon, L. Schiltz, and J. Xuan, Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb???MyoD pathways in muscle regeneration, Brain, vol.129, issue.4, pp.996-1013, 2006.
DOI : 10.1093/brain/awl023

H. Li, W. Watford, C. Li, A. Parmelee, and M. Bryant, Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development, Journal of Clinical Investigation, vol.117, issue.5, pp.1314-1323, 2007.
DOI : 10.1172/JCI31222DS1

L. Chen, D. Liu, and Z. Songyang, Telomere Maintenance through Spatial Control of Telomeric Proteins, Molecular and Cellular Biology, vol.27, issue.16, pp.5898-5909, 2007.
DOI : 10.1128/MCB.00603-07

C. Farr, M. Stevanovic, E. Thomson, P. Goodfellow, and H. Cooke, Telomere???associated chromosome fragmentation: applications in genome manipulation and analysis, Nature Genetics, vol.47, issue.4, pp.275-282, 1992.
DOI : 10.1038/347674a0

J. Vilquin, Myoblast transplantation: clinical trials and perspectives. Mini-review, Acta Myol, vol.24, pp.119-127, 2005.

J. Espada, E. Ballestar, M. Fraga, A. Villar-garea, and A. Juarranz, Human DNA Methyltransferase 1 Is Required for Maintenance of the Histone H3 Modification Pattern, Journal of Biological Chemistry, vol.33, issue.35, pp.37175-37184, 2004.
DOI : 10.1038/ng1146

D. Loukinov, E. Pugacheva, S. Vatolin, S. Pack, and H. Moon, BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma, Proceedings of the National Academy of Sciences, vol.26, issue.19, pp.6806-6811, 2002.
DOI : 10.1093/nar/26.19.4413

W. Stedman, H. Kang, S. Lin, J. Kissil, and M. Bartolomei, Cohesins localize with CTCF at the KSHV latency control region and at cellular c-myc and H19/Igf2 insulators, The EMBO Journal, vol.76, issue.4, pp.654-666, 2008.
DOI : 10.1007/978-3-642-56352-2_4