This paper investigates the nuclear localization of human telomeres and, specifically, the 4q35 subtelomere mutated in facioscapulohumeral dystrophy (FSHD). FSHD is a common muscular dystrophy that has been linked to contraction of D4Z4 tandem repeats, widely postulated to affect distant gene expression. Most human telomeres, such as 17q and 17p, avoid the nuclear periphery to reside within the internal, euchromatic compartment. In contrast, 4q35 localizes at the peripheral heterochromatin with 4p more internal, generating a reproducible chromosome orientation that we relate to gene expression profiles. Studies of hybrid and translocation cell lines indicate this localization is inherent to the distal tip of 4q. Investigation of heterozygous FSHD myoblasts demonstrated no significant displacement of the mutant allele from the nuclear periphery. However, consistent association of the pathogenic D4Z4 locus with the heterochromatic compartment supports a potential role in regulating the heterochromatic state and makes a telomere positioning effect more likely. Furthermore, D4Z4 repeats on other chromosomes also frequently organize with the heterochromatic compartment at the nuclear or nucleolar periphery, demonstrating a commonality among chromosomes harboring this subtelomere repeat family.
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25 October 2004
Article|
October 25 2004
The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres
Rose Tam,
Rose Tam
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
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Kelly P. Smith,
Kelly P. Smith
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
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Jeanne B. Lawrence
Jeanne B. Lawrence
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
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Rose Tam
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
Kelly P. Smith
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
Jeanne B. Lawrence
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
Correspondence to J.B. Lawrence: [email protected]
Abbreviations used in this paper: FSHD, facioscapulohumeral dystrophy; TPE, telomere position effect.
Received:
March 23 2004
Accepted:
September 02 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 167 (2): 269–279.
Article history
Received:
March 23 2004
Accepted:
September 02 2004
Citation
Rose Tam, Kelly P. Smith, Jeanne B. Lawrence; The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres . J Cell Biol 25 October 2004; 167 (2): 269–279. doi: https://doi.org/10.1083/jcb.200403128
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