Speaker: Dr. Jean-François Couture Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Canada Ash2L; a link between histone methylation and homeobox genes expression. Histone proteins are decorated by a large array of post-transcriptional modifications including acetylation, methylation and phosphorylation. These modifications, alone or in combination, control a plethora of cellular processes that include transcription, DNA-strand break repair and chromosomal stability. Among those, methylation of histone H3 on Lys-4 (H3K4) has been recognized has an important modifications deposited at the promoter regions of different genes. Recognized by various effectors proteins, H3K4 methylation is linked to transcriptional activation. Although this modification is essential for several biological processes, the mechanisms regulating the positioning of a H3K4 methyltransferase to specific gene promoters have remained poorly defined. Research in my laboratory focuses on the histone H3K4 methyltransferase myeloid lymphoma leukemia (MLL) protein complex. MLL is a structurally complex protein composed of several functional domains such as plant homeodomains, AT-hook motifs and a SET domain. Consistent with its complexity, interactions of MLL with its regulatory proteins are keys for stimulating MLL enzymatic activity or controlling its cellular localization. Very recent discoveries in my laboratory have identified that Ash2L, an essential subunit of the MLL complex, bridges MLL to specific transcription factors. In addition, we have identified that Ash2L harbors an atypical DNA binding domain that folds as an extended helix-wing-helix domain. We are currently dissecting the mechanism by which Ash2L interacts with different transcription factors and links MLL or other H3K4 methyltransferases to a large number of functionally divergent promoters. Overall, our preliminary results suggest that Ash2L could link transcription factors to histone H3K4 methyltransferase complexes and act as a molecular switch between transcription and epigenetic modifications.