Functional relationship between cell fate decision and epigenetic control of gene expression of the chromosome

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670465
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: KITAMURA TOSHIO 東京大学, 医科学研究所, 教授 (20282527)
• Co-Investigator(Kenkyū-buntansha): INABA Toshiya 広島大学, 原爆放射線医科学研究所, 教授 (60281292) ; MATSUI Hirotaka 熊本大学, 大学院生命科学研究部, 教授 (60379849)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: エピジェネティクス / 細胞分化 / ヒストン修飾 / スプライシング

Outline of Final Research Achievements

A human leukemic cell line HL60 differentiates to granulocytes and monocytes in response to retinoic acid and vitamin D3 treatment, respectively. In this project, we performed RNAseq analysis serially, and searched genes whose expression increases during the differentiation processes. In the results, we have identified several such genes. However, in contrast to our prediction, these genes do not localize in the neighborhood of chromosomes. Therefore, to investigate the roles of epigenetics in the differentiation of HL60 cells, we next knocked down an epigenetic factor ASXL1 involved in histone modification and analyzed the relationship between cell differentiation and histone modification. We have found that ASXL1 knockdown decreases trimethylation of histone H3K4 and H3K27 leading to inhibition of the differentiation of HL60 cells.

Free Research Field

分子生物学・血液腫瘍学