Document Detail

Methylation of the FSHD syndrome-linked subtelomeric repeat in normal and FSHD cell cultures and tissues.
MedLine Citation:
PMID:  11708861     Owner:  NLM     Status:  MEDLINE    
Facioscapulohumeral muscular dystrophy (FSHD) has an unusual molecular etiology. In a putatively heterochromatic subtelomeric region of each chromosome 4 homologue (4q35), unaffected individuals have 11 to about 95 tandem copies of a complex 3.3-kb repeat (D4Z4). Most FSHD patients have less than 10 copies at one allelic 4q35. This has been proposed to lead to the loss of heterochromatinization and, thereby, inappropriate gene expression by position effects, explaining the dominant nature of FSHD and the role of a decreased number of copies of D4Z4 at 4q35 but not at 10q26. Consistent with the proposed heterochromatinization of this repeat, by Southern blot analysis, we found that SmaI, MluI, SacII, and EagI sites in D4Z4 are highly methylated in normal and FSHD cell lines and somatic tissues, including skeletal muscle. Like repeated DNA sequences in the juxtacentromeric heterochromatin of chromosomes 1, 9, and 16, D4Z4 was hypomethylated at numerous CpGs in sperm and in cell lines from patients with an unrelated DNA methyltransferase deficiency syndrome (ICF; immunodeficiency, centromeric region instability, facial anomalies) in contrast to its hypermethylation in non-ICF postnatal somatic tissues. Our data on FSHD samples suggest that the disease-associated 4q35 D4Z4 repeats, which constitute a small percentage of the total D4Z4 repeats, are not generally hypomethylated relative to the other repeats of this sequence. However, in individuals not affected with FSHD, the hypermethylation of tandem, high-copy-number D4Z4 repeats might help stabilize heterochromatinization at allelic 4q35 regions just as hypermethylation elsewhere in the genome has been linked to chromatin compaction.
F Tsien; B Sun; N E Hopkins; V Vedanarayanan; D Figlewicz; S Winokur; M Ehrlich
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular genetics and metabolism     Volume:  74     ISSN:  1096-7192     ISO Abbreviation:  Mol. Genet. Metab.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-15     Completed Date:  2002-01-08     Revised Date:  2008-08-29    
Medline Journal Info:
Nlm Unique ID:  9805456     Medline TA:  Mol Genet Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  322-31     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Human Genetics Program, School of Medicine, Tulane University, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
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MeSH Terms
Bacterial Proteins / metabolism
Binding Sites / genetics
Blotting, Southern
Cells, Cultured
Chromosomes, Human, Pair 4 / genetics
DNA / genetics,  metabolism
DNA Methylation*
Deoxyribonucleases, Type II Site-Specific / metabolism
Muscular Dystrophy, Facioscapulohumeral / genetics*
Tandem Repeat Sequences / genetics*
Telomere / genetics*
Grant Support
Reg. No./Substance:
0/Bacterial Proteins; 9007-49-2/DNA; EC 3.1.21.-/endodeoxyribonuclease MluI; EC 3.1.21.-/endodeoxyribonuclease XmaIII; EC type II deoxyribonucleases; EC type II deoxyribonucleases; EC, Type II Site-Specific

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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