UMMS Affiliation

Department of Cell Biology

Publication Date


Document Type



Alleles; Cell Line; Cell Nucleus; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 4; Fibroblasts; Heterochromatin; Heterozygote; Humans; Image Processing, Computer-Assisted; In Situ Hybridization; Interphase; Muscles; Muscular Dystrophy, Facioscapulohumeral; Mutation; Nuclear Proteins; Protein Structure, Tertiary; Proteins; Telomere


Cell Biology | Life Sciences | Medicine and Health Sciences


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.

DOI of Published Version



J Cell Biol. 2004 Oct 25;167(2):269-79. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of cell biology

Related Resources

Link to Article in PubMed

PubMed ID




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