Emerging role of enhancer RNA in NRF2-dependent human HO-1 gene induction

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860202
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Hirosaki University
• Principal Investigator: MARUYAMA Atsushi 弘前大学, 医学(系)研究科(研究院), 助教 (10431438)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ヘムオキシゲナーゼー１ / NRF2 / ノンコーディングRNA / 転写制御 / 酸化ストレス

Outline of Final Research Achievements

Emerging evidence indicates that enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, play important roles in the regulation of gene expression. However, it remains unknown whether eRNAs are involved in the human heme oxygenase-1 gene (HO-1) induction. HO-1 possesses two distantly located enhancers called E2 and E1 enhancers to regulate its transcription.
In this study, I demonstrated that eRNAs are transcribed from the human HO-1 enhancers. Focusing on E2-derived enhancer RNA (eRNA E2), I found eRNA E2 is induced in response to HO-1 substrate heme and oxidative stress-causing reagents such as diethyl maleate (DEM) in an NRF2-dependent manner. I also found DEM-induced HO-1 expression was selectively down-regulated by knockdown of the eRNA E2. Furthermore, DEM-induced Pol II binding to human HO-1 regions is attenuated in eRNA E2 knockdown cells. These results indicate that eRNA E2 is functional and required for the induction of HO-1.

Free Research Field

生化学、分子生物学