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Publication year
2004Source
Human Molecular Genetics, 13, 17, (2004), pp. 1857-71ISSN
Publication type
Article / Letter to editor
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Organization
Neurology
Human Genetics
Journal title
Human Molecular Genetics
Volume
vol. 13
Issue
iss. 17
Page start
p. 1857
Page end
p. 71
Subject
UMCN 3.1: Neuromuscular development and genetic disordersAbstract
Facioscapulohumeral muscular dystrophy (FSHD) may be a new member of the class of neuromuscular diseases (NMD) due to defects in the nuclear envelope. Unlike other NMDs with primary defects in nuclear envelope proteins, however, FSHD may result from inappropriate chromatin interactions at the envelope. 3D Immuno-FISH and a novel method of 3D by 2D analysis using NucProfile were developed to examine nuclear organization of the FSHD genomic region. In contrast to most other telomeres, the FSHD region at 4q35.2 localizes to the nuclear periphery. This localization is consistent in normal myoblasts, myotubes, fibroblasts and lymphoblasts, does not vary significantly throughout the cell cycle, and is independent of chromosome territory effects. The nuclear lamina protein lamin A/C is required for FSHD region chromatin localization to the nuclear envelope, as the association is lost in lamin A/C null fibroblasts. As both normal and affected alleles (deleted for the subtelomeric repeat D4Z4) localize to the nuclear periphery, FSHD likely arises instead from improper interactions with transcription factors or chromatin modifiers at the nuclear envelope. Interestingly, it is not D4Z4 itself that mediates interaction with the envelope, as sequences proximal to D4Z4 (i.e. D4S139) localize closer to the nuclear periphery, perhaps accounting for the chromosome 4 specificity of the disease.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122537]
- Faculty of Medical Sciences [90373]
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