Genetic regulation of CFTR expression
(Marie-Catherine Romey-Chatelain)
While reasonable progress has been made toward finding the different CFTR-associated functions and dysfunctions, little is known about the regulation of CFTR expression in both epithelial and non-epithelial tissues. Early work aimed at understanding the precise control of CFTR gene expression had some success in identifying a few functional elements. However, understanding the mechanisms that direct CFTR expression remains largely unknown. Thus, more effort is needed to improve our current knowledge of the sites and signals that modulate CFTR expression. We have initially focused our attention on the delineation of regulatory motifs associated to naturally occurring sequence variations that we previously identified in the minimal CFTR promoter. Our current aim is to characterize the function of different transcription factors, and to elucidate various interaction networks and signalling mechanisms controlling CFTR transcriptional activity, in molecular detail. Ultimately, our long-term goal is to use this knowledge to develop more appropriate and specific gene therapy for CF.
Expertise
Members of this program have expertise in areas that include chromatin, regulation of transcription via ubiquitous and cell-specific transcription factors binding, protein-protein interactions, cell signalling mechanisms and post-transcriptional modifications studies, such as acetylation. Our current approaches include computational analyses, expression vectors constructs, mammalian cell transfection assays, FACS analysis, indirect immunofluorescence and confocal microscopy, in vitro (EMSA) and in vivo (ChIP) DNA-protein interactions analyses, protein-protein interactions analyses (coIP, mammalian two-hybrid system), acetylation assays and the use of epigenetic tools such as siRNA to modulate gene expression.
