Experimental and bioinformatic characterisation of the promoter region of the Marfan syndrome gene, FBN1

Summers, Kim M., Bokil, Nilesh J., Baisden, John M., West, Malcolm J., Sweet, Matthew J., Raggatt, Liza J. and Hume, David A. (2009) Experimental and bioinformatic characterisation of the promoter region of the Marfan syndrome gene, FBN1. Genomics, 94 4: 233-240. doi:10.1016/j.ygeno.2009.06.005

Author Summers, Kim M.
Bokil, Nilesh J.
Baisden, John M.
West, Malcolm J.
Sweet, Matthew J.
Raggatt, Liza J.
Hume, David A.
Title Experimental and bioinformatic characterisation of the promoter region of the Marfan syndrome gene, FBN1
Journal name Genomics   Check publisher's open access policy
ISSN 0888-7543
Publication date 2009-10
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.ygeno.2009.06.005
Volume 94
Issue 4
Start page 233
End page 240
Total pages 8
Editor J. Quackenbush
Place of publication Maryland Heights, M.O., U.S.A.
Publisher Academic Press (Elsevier Science)
Collection year 2010
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
060408 Genomics
Formatted abstract
Mutations in the FBN1 gene, encoding the extracellular matrix protein fibrillin-1, result in the dominant connective tissue disease Marfan syndrome. Marfan syndrome has a variable phenotype, even within families carrying the same FBN1 mutation. Differences in gene expression resulting from sequence differences in the promoter region of the FBN1 gene are likely to be involved in causing this phenotypic variability. In this report, we present an analysis of FBN1 transcription start site (TSS) use in mouse and human tissues. We found that transcription of FBN1 initiated primarily from a single CpG-rich promoter which was highly conserved in mammals. It contained potential binding sites for a number of factors implicated in mesenchyme differentiation and gene expression. The human osteosarcoma line MG63 had high levels of FBN1 mRNA and secreted fibrillin-1 protein to form extracellular matrix fibres. The human embryonic kidney line HEK293 and two breast cancer lines MCF7 and MDA-MB-231 had levels of FBN1 mRNA 1000 fold lower and produced negligible amounts of fibrillin-1 protein. Therefore MG63 appears to be the optimal cell line for examining tissue-specific, biologically relevant promoter activity for FBN1. In reporter assays, the conserved promoter region was more active in MG63 cells than in non-FBN1-expressing lines but additional elements outside the proximal promoter are probably required for optimal tissue-specific expression. Understanding the regulation of the FBN1 gene may lead to alternative therapeutic strategies for Marfan syndrome.
Keyword Marfan syndrome
Gene expression
Dominant genetic conditions
Reporter genes
Promoter regions
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Author Baisden accredited to SCMB as per the pub. by-line. JJF 16.4.10

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 24 Jan 2010, 00:04:27 EST