Transcriptional profiling of the human fibrillin/LTBP gene family, key regulators of mesenchymal cell functions

Davis, Margaret R., Andersson, Robin, Severin, Jessica, de Hoon, Michiel, Bertin, Nicolas, Baillie, J. Kenneth, Kawaji, Hideya, Sandelin, Albin, Forrest, Alistair R.R., Summers, Kim M. and for the FANTOM Consortium (2014) Transcriptional profiling of the human fibrillin/LTBP gene family, key regulators of mesenchymal cell functions. Molecular Genetics and Metabolism, 112 1: 73-83. doi:10.1016/j.ymgme.2013.12.006


Author Davis, Margaret R.
Andersson, Robin
Severin, Jessica
de Hoon, Michiel
Bertin, Nicolas
Baillie, J. Kenneth
Kawaji, Hideya
Sandelin, Albin
Forrest, Alistair R.R.
Summers, Kim M.
for the FANTOM Consortium
Title Transcriptional profiling of the human fibrillin/LTBP gene family, key regulators of mesenchymal cell functions
Journal name Molecular Genetics and Metabolism   Check publisher's open access policy
ISSN 1096-7206
1096-7192
Publication date 2014-05
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.ymgme.2013.12.006
Open Access Status DOI
Volume 112
Issue 1
Start page 73
End page 83
Total pages 11
Place of publication Waltham, MA, United States
Publisher Academic Press
Collection year 2015
Language eng
Formatted abstract
The fibrillins and latent transforming growth factor binding proteins (LTBPs) form a superfamily of extracellular matrix (ECM) proteins characterized by the presence of a unique domain, the 8-cysteine transforming growth factor beta (TGFβ) binding domain. These proteins are involved in the structure of the extracellular matrix and controlling the bioavailability of TGFβ family members. Genes encoding these proteins show differential expression in mesenchymal cell types which synthesize the extracellular matrix. We have investigated the promoter regions of the seven gene family members using the FANTOM5 CAGE database for human. While the protein and nucleotide sequences show considerable sequence similarity, the promoter regions were quite diverse. Most genes had a single predominant transcription start site region but LTBP1 and LTBP4 had two regions initiating different transcripts. Most of the family members were expressed in a range of mesenchymal and other cell types, often associated with use of alternative promoters or transcription start sites within a promoter in different cell types. FBN3 was the lowest expressed gene, and was found only in embryonic and fetal tissues. The different promoters for one gene were more similar to each other in expression than to promoters of the other family members. Notably expression of all 22 LTBP2 promoters was tightly correlated and quite distinct from all other family members. We located candidate enhancer regions likely to be involved in expression of the genes. Each gene was associated with a unique subset of transcription factors across multiple promoters although several motifs including MAZ, SP1, GTF2I and KLF4 showed overrepresentation across the gene family. FBN1 and FBN2, which had similar expression patterns, were regulated by different transcription factors. This study highlights the role of alternative transcription start sites in regulating the tissue specificity of closely related genes and suggests that this important class of extracellular matrix proteins is subject to subtle regulatory variations that explain the differential roles of members of this gene family.
Keyword Fibrillin
Latent transforming growth factor β binding protein
Transcription start sites
Gene regulation
Extracellular matrix
Promoter
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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