July 6 2018
We would like to inform you that the 40th IRCMS Seminar has been scheduled as below. We would be pleased to see many of you participating in the seminar.
Date : July 17, 2018 (Tue)
Time : 16:00 - 17:00
Venue : 1F Meeting Lounge, International Research Center for Medical Sciences (IRCMS)
Speaker : Dr. Takayuki Hoshii, Ph.D.
Department of Pediatric Oncology, Dana-Farber Cancer Institute,
Division of Hematology / Oncology, Boston Children's Hospital
Harvard Medical School
Title: Identification and targeting of the transcriptional vulnerabilities in leukemia
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 a 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. We also identified FLOS subunits for DNA repair-associated gene expression in S phase. These data indicate a connection between the chromatin regulator SETD1A and the DNA damage response, and suggests that targeting newly identified SETD1A complexes may represent a therapeutic opportunity for AML and other cancers.