Regulation of Treacher Collins Syndrome TCOF1 gene

Virginia Commonwealth University, Richmond VA

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Abstract

DESCRIPTION (provided by applicant): Characterization of the Treacher Collins Syndrome gene (TCOF1) regulatory region is necessary to understanding the etiology of disease: expression of TCOF1 is tissue-and temporal-restricted during early embryonic development although it is not known how TCOF1 functions in health or in disease. The main goal of this project is to determine the core sequences necessary and sufficient to direct transcription of the TCOF1 gene and will be accomplished in three specific aims, including 1. to determine the minimal promoter necessary to direct expression of a reporter plasmid in neural crest-like cells in transfection studies, and the comparative expression of reporter constructs of different lengths; 2. to test the hypothesis that specific putative cis-binding sites within the promoter are essential to expression through mutation analysis; and 3. to determine if the minimal promoters can direct correct temporal and tissue-specific expression of a reporter gene in vivo in a mouse model. Once characterized, mutations within the promoter region of TCS patients can be identified and the TCOF1 promoter may prove useful in promoter characterization of other genes with tissue- and developmental-stage specific expression and/or in gene therapy in individuals with risk for TCS.