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The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres.

Tam R, Smith KP, Lawrence JB - J. Cell Biol. (2004)

Bottom Line: Studies of hybrid and translocation cell lines indicate this localization is inherent to the distal tip of 4q.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

ABSTRACT
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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The spatial orientation of chromosomes 4 and 17 correlates with the density of expression along their axes. (A) Model depicting the spatial arrangement of chromosomes 4 and 17. (B) Distribution of gene density and expression for each chromosome (data reproduced with permission from Versteeg et al., 2003).
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fig4: The spatial orientation of chromosomes 4 and 17 correlates with the density of expression along their axes. (A) Model depicting the spatial arrangement of chromosomes 4 and 17. (B) Distribution of gene density and expression for each chromosome (data reproduced with permission from Versteeg et al., 2003).

Mentions: Fig. 4 A summarizes our findings for the organization of chromosome 4 and contrasts it with chromosome 17. Results demonstrate that a fundamental aspect of chromosome organization in human cells can involve a defined three-dimensional chromosome orientation for a specific chromosome. This organization shows an interesting relationship with recent data on the profiles of gene density and expression over the chromosome (Fig. 4 B; Versteeg et al., 2003). As considered further in the Discussion, the orientation of chromosome 4 is not simply mirrored by differences in gene density on 4q versus 4p, but shows an intriguing correlation with gene expression.


The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres.

Tam R, Smith KP, Lawrence JB - J. Cell Biol. (2004)

The spatial orientation of chromosomes 4 and 17 correlates with the density of expression along their axes. (A) Model depicting the spatial arrangement of chromosomes 4 and 17. (B) Distribution of gene density and expression for each chromosome (data reproduced with permission from Versteeg et al., 2003).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172553&req=5

fig4: The spatial orientation of chromosomes 4 and 17 correlates with the density of expression along their axes. (A) Model depicting the spatial arrangement of chromosomes 4 and 17. (B) Distribution of gene density and expression for each chromosome (data reproduced with permission from Versteeg et al., 2003).
Mentions: Fig. 4 A summarizes our findings for the organization of chromosome 4 and contrasts it with chromosome 17. Results demonstrate that a fundamental aspect of chromosome organization in human cells can involve a defined three-dimensional chromosome orientation for a specific chromosome. This organization shows an interesting relationship with recent data on the profiles of gene density and expression over the chromosome (Fig. 4 B; Versteeg et al., 2003). As considered further in the Discussion, the orientation of chromosome 4 is not simply mirrored by differences in gene density on 4q versus 4p, but shows an intriguing correlation with gene expression.

Bottom Line: Studies of hybrid and translocation cell lines indicate this localization is inherent to the distal tip of 4q.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus