Document Detail

FRG2, an FSHD candidate gene, is transcriptionally upregulated in differentiating primary myoblast cultures of FSHD patients.
MedLine Citation:
PMID:  15520407     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is associated with partial deletion of the subtelomeric D4Z4 repeat array on chromosome 4qter. This chromosomal rearrangement may result in regional chromatin relaxation and transcriptional deregulation of genes nearby. METHODS AND RESULTS: Here we describe the isolation and characterisation of FRG2, a member of a chromosomally dispersed gene family, mapping only 37 kb proximal to the D4Z4 repeat array. Homology and motif searches yielded no clues to the function of the predicted protein. FRG2 expression is undetectable in all tissues tested except for differentiating myoblasts of FSHD patients, which display low, yet distinct levels of FRG2 expression, partly from chromosome 4 but predominantly originating from its homologue on chromosome 10. However, in non-FSHD myopathy patients only distantly related FRG2 homologues are transcribed, while differentiating myoblasts from healthy controls fail to express any member of this gene family. Moreover, fibroblasts of FSHD patients and control individuals undergoing forced Ad5-MyoD mediated myogenesis show expression of FRG2 mainly originating from chromosome 10. Luciferase reporter assays show that the FRG2 promoter region can direct high levels of expression but is inhibited by increasing numbers of D4Z4 repeat units. Transient transfection experiments with FRG2 fusion-protein constructs reveal nuclear localisation and apparently FRG2 overexpression causes a wide range of morphological changes. CONCLUSION: The localisation of FRG2 genes close to the D4Z4 repeats on chromosome 4 and 10, their transcriptional upregulation specifically in FSHD myoblast cultures, potential involvement in myogenesis, and promoter properties qualify FRG2 as an attractive candidate for FSHD pathogenesis.
T Rijkers; G Deidda; S van Koningsbruggen; M van Geel; R J L F Lemmers; J C T van Deutekom; D Figlewicz; J E Hewitt; G W Padberg; R R Frants; S M van der Maarel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medical genetics     Volume:  41     ISSN:  1468-6244     ISO Abbreviation:  J. Med. Genet.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-02     Completed Date:  2005-04-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985087R     Medline TA:  J Med Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  826-36     Citation Subset:  IM    
Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AY714545;  AY744466
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MeSH Terms
Amino Acid Sequence
Base Sequence
Cell Differentiation
Cells, Cultured
Chromosomes, Human, Pair 10 / genetics
Chromosomes, Human, Pair 4 / genetics
Genetic Predisposition to Disease
Molecular Sequence Data
Muscle Development
Muscular Dystrophy, Facioscapulohumeral / genetics*
Myoblasts, Skeletal / chemistry,  cytology,  metabolism*
Promoter Regions, Genetic
Proteins / analysis,  genetics*,  metabolism
Transcriptional Activation*
Reg. No./Substance:
0/FRG2 protein, human; 0/Proteins

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