Analyzing transcription factor network and chromatin regulation during epithelial-to-mesenchymal transition

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06952
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: WATANABE KAZUHIDE 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, 上級研究員 (40749397)
• Co-Investigator(Kenkyū-buntansha): 須田 年生 熊本大学, 国際先端医学研究機構, 卓越教授 (60118453)
• Research Collaborator: Dai Xing University of California, Irvine
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: EMT / TGFbeta / ZEB1 / CAGE / ATAC-seq / chromatin states / transcription factor / epithelial cell

Outline of Final Research Achievements

In this study, we explored how the gene expression and chromatin status are controlled during epithelial-mesenchymal transition (EMT). In EMT, a cell loses epithelial (E) phenotype and simultaneously acquires mesenchymal (M) phenotype. Our study discovered that the transcription factor ZEB1 plays an important role in controlling reciprocal regulation of E and M phenotypes. As a molecular mechanism, ZEB1 induces closed chromatin states at major E gene loci, while M gene loci are categorized into ZEB1-dependent and independent groups. We constructed a mathematical model based on a hypothesis that "reciprocal changes in E and M genes during EMT are regulated by a ZEB1-TGFbeta positive feedback loop" and succeeded to predict gene expresion changes in EMT.

Free Research Field

細胞生物学