|開催日時：||2017年12月14日 17：00 ～ 18：30|
|所属：||Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children’s Hospital, Harvard Medical School
|演題：||A non-catalytic function of MLL/SET H3K4 methyltransferase in acute myeloid leukemia cells|
Epigenetic regulations of chromatin state by mediator enzymes play an important role in the control of gene expression during normal development and cancer. The disease-specific transcriptional regulation is an attractive therapeutic target and there is an increasing demand for identification of target molecule as well as development of epigenetic drugs. MLL/SET methyltransferases catalyze methylation of histone 3 lysine 4 and play critical roles in development and cancer. We assessed MLL/SET proteins and found that SETD1A is required for survival of acute myeloid leukemia (AML) cells. Mutagenesis studies and CRISPR-Cas9 domain screening, showed the enzymatic SET domain is not necessary for AML cell survival but that a newly identified region, termed the FLOS (Functional Location on SETD1A) domain, is indispensable. The FLOS domain acts as a Cyclin K-association site that is required for chromosomal recruitment of Cyclin K, and for DNA repair-associated gene expression in S phase. These data identify a connection between the chromatin regulator SETD1A and the DNA damage response that is independent of histone methylation, and suggests that targeting SETD1A and Cyclin K complexes may represent a therapeutic opportunity for AML and potentially other cancers.
|世話人：||〇中西 真 （癌防御シグナル分野）
北村 俊雄 （細胞療法分野）