2012 Fiscal Year Final Research Report

Novel mechanism regulating timing of cardiovascular cells with molecular linkage between PKA signaling and epigenome regulation

Research Project

Project/Area Number	24659389
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Circulatory organs internal medicine
Research Institution	Kyoto University
Principal Investigator	YAMASHITA Jun 京都大学, iPS 細胞研究所, 教授 (50335288)
Project Period (FY)	2012
Keywords	エピジェネティクス / ES細胞 / 分化(4) G9a / PKA / ヒストンメチル化
Research Abstract	Currently, it is still impossible to manipulate the timing and velocity of embryonic stem cell differentiation. This study is aiming at elucidation of molecular and cellular mechanisms of regulation for timing and velocity of stem cell differentiation. We demonstrated that activation of protein kinase A (PKA) accelerates differentiation velocity to induce approximately 2-times earlier appearance of mesoderm and other germ layer cells, reciprocally correlated with the earlier disappearan ce of pluripotent markers after ESC differentiation. PKA activation increased protein expression of G9a, a H3K9 methyltransferase, along with earlier H3K9 dimethylation and DNA methylation in Oct3/4 and Nanog gene promoters. We thus reported this novel mechanism regulating differentiation timing of embryonic stem cells（Yamamizu, Cell Stem Cell, 2012）

(3 results)