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Regulation of gene expression by the TGF-beta growth factors

Applicant Mermod Nicolas
Number 100746
Funding scheme Project funding (Div. I-III)
Research institution Institut des sciences et ingénierie chimiques EPFL - SB - ISIC
Institution of higher education University of Lausanne - LA
Main discipline Molecular Biology
Start/End 01.04.2003 - 31.07.2006
Approved amount 191'090.00
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All Disciplines (2)

Discipline
Molecular Biology
Genetics

Keywords (6)

Gene transcription; Regulation; Signaling; Growth factors; Fibroblasts; Fibrosis

Lay Summary (English)

Lead
Lay summary
The TGF-? peptides are growth factors that regulate cell proliferation and the accumulation of extra-cellular matrix proteins in processes such as wound healing and fibrosis. They act in part by regulating specific transcription factors. However, the ptrasncriptionathways and intermediates involved in such regulatory processes are still poorly understood.We have found that TGF-?1 controls the activity of the CTF-1 transcription factor, which in turn regulates the expression of several extracellular matrix proteins in primary fibroblasts. In knock-out mice, the lack of CTF-1 leads to improper development and morphogenesis that resemble a family of human diseases called ectodermal dysplasia. In lower eukaryotes, we found that CTF-1 fusion proteins act as chromosomal boundary element that prevents the spreading of a silent chromatin structure. Thus, we conclude that CTF-1 may be part of a regulatory pathway that connects the TGF-? signals to the chromatin structure-mediated regulation of genes involved in tissue remodeling, and that its disregulation may be linked to disease in humans.At present, we are trying to further decifer which developmental events are not regulated properly in the absence of CTF-1, and to identify CTF-1 target genes which improper expression may lead to the oberved disease-like phenotypes. We expect that these studies will lead to better understanding of the molecular mechanisms of several human diseases, which may in turn contribute to the possible development of better diagnostic or therapeutic strategies.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
59370 Regulation of gene expression by growth factors 01.04.2000 Project funding (Div. I-III)

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