東京大学医科学研究所

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学友会セミナー

学友会セミナー:2017年12月14日

開催日時: 2017年12月14日 17:00 ~ 18:30
開催場所: 2号館小講義室
講師: 星居 孝之
所属: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children’s Hospital, Harvard Medical School
Scientist I
演題: A non-catalytic function of MLL/SET H3K4 methyltransferase in acute myeloid leukemia cells
概要:

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)