Speaker: Dr. Alexandre Blais Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada A functional genomic analysis of Six transcription factors during myogenesis Myogenesis is controlled in large part at the transcriptional level through the concerted action of several transcription factors. Previously, we have applied functional genomic approaches to establish a map of transcriptional regulatory interactions centered around the Myogenic Regulatory Factors (MRFs). Based on the results of this work, we hypothesized that MRFs control the expression of their target genes by cooperating with a number of additional transcription factors, including Six homeodomain transcription factors. Certain members of the Six family are important for muscle development: mice devoid of Six1 are characterized by defective embryonic myogenesis, a phenotype which is exacerbated in the Six1;Six4 double knock-out animals. However, understanding of the molecular mode of action of these factors is far from complete. Furthermore, the role they play in late events of myogenesis and muscle regeneration have drawn little attention. We have undertaken a genomic characterization of the function of Six transcription factors in a model of myogenic regeneration. We confirm the prediction that Six and MRFs share common target genes and that they regulate the expression of these genes in a combinatorial fashion. Our work suggests a further level of regulation of MRF function and myogenesis and brings new light to the impaired myogenesis phenotype of Six knock-out mice.