Regulation mechanism of a transcription cycle by static/dynamic structural analyses

2016 Fiscal Year Final Research Report

• Project Area: Integral understanding of the mechanism of transcription cycle through quantitative, high-resolution approaches
• Project/Area Number: 24118005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Yokohama City University
• Principal Investigator: OGATA Kazuhiro 横浜市立大学, 医学研究科, 教授 (90260330)
• Co-Investigator(Renkei-kenkyūsha): SHIINA Masaaki 横浜市立大学, 医学部, 助教 (30347299) ; HAMADA Keisuke 横浜市立大学, 医学部, 助教 (00344052)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: 転写制御 / 転写因子 / 化学修飾

Outline of Final Research Achievements

Signal transduction transfers cellular environmental information to nucleus via chemical modifications of proteins and finally modulates transcription profile of the cell. To reveal the molecular mechanism of conversion of the information from chemical modification to transcriptional modulation, we employed static and dynamic structural analyses of higher-ordered transcription factors(TF)-DNA complexes. We found that phosphorylation of the intrinsically disordered region of the transcription factor Ets1 induces a non-DNA-binding conformer of Ets1 itself. On the tcrα enhancer, the partner TF Runx1 selects the specific Ets1 conformer that is refractory to effect of phosphorylation, resisting the inhibitory effect of phosphorylation of Ets1 and specifically keeping the tcrα gene transcription active, while many of other Ets1-target genes turn off. This transcription switch may enable fine regulation responding to cellular environments including development and proliferation signals.

Free Research Field

生化学、構造生物学