BEGIN:VCALENDAR BEGIN:VEVENT SUMMARY:USC PSOC Monthly Seminar Series DESCRIPTION:Speaker: Jonathan Licht, M.D.,, Jonathan Licht, M.D., Professor of Hematology/Oncology, Northwestern University, Feinberg School of Medicine Talk Title: The MMSET, A Histone Methyl Transferase Alters Chromatin Structure And Gene Expression In Multiple Myeloma Abstract: The multiple myeloma SET domain (MMSET) gene is a recurrent chromosomal partner in the t(4;14) translocation-associated multiple myeloma, and MMSET levels are dramatically elevated in these patients relative to other myeloma cases and normal cells. MMSET contains several domains commonly found in chromatin regulators including the PHD domain, PWWP domain and SET domain; responsible for enzymatic activity. What histone residues are methylated by MMSET in vivo has been uncertain. To determine how MMSET affects chromatin in vivo and to identify genes directly regulated by MMSET, we created a loss-of-function model, engineering t(4;14)+ KMS11 cells with a tetracycline-inducible shRNA specific for MMSET. Upon loss of MMSET expression, there was a striking decrease of trimethylated histone 3, lysine 36 (H3K36me3), a mark of transcriptional elongation and repression of extraneous transcription. Loss of MMSET expression was associated with a strong increase in H3K27me3, a chromatin mark associated with gene repression. To determine the genes regulated by MMSET and the importance of histone methylation in MMSET activity, we profiled gene expression in both gain and loss-of-function systems. Functional annotation of genes bound and regulated by MMSET showed over-representation of genes implicated in regulation of cell death/p53 pathway (BAX, BCL2, CASP6, ATM), cell cycle (CCNE2, E2F2, TP53INP1, CDC25A) and integrin signaling (ACTB, CDC42, ITGAL). The effect of MMSET on integrin signaling is of particular interest given that loss of MMSET expression or repletion of KMS11-TKO cells with MMSET gene alters cell adhesion properties. These data indicate that MMSET may regulate genes in a histone methyl transferase dependent and independent manner. Furthermore, MMSET target genes may be both activated and repressed upon changes in MMSET levels, indicating a complex interplay with the transcriptional machinery, likely though interactions with other transcriptional co-factors. \n \n Location: Harkness Auditorium, CSC 250, IGM Building\n \n For additional information contact: 323-442-3849 or 323-442-2596 Biography: Jonathan Licht, M.D.,Johanna Dobe Professor & Chief, Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine Host: Dr. Parag Mallick, Center for Applied Molecular Medicine DTSTART:20101217T113000 LOCATION:HAR URL;VALUE=URI: DTEND:20101217T130000 END:VEVENT END:VCALENDAR