Mechanisms underlying regulation of mammalian neuronal differentiation via histone acetylation

2017 Fiscal Year Final Research Report

• Project/Area Number: 26860860
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Osama Woman's and Children's Hospital
• Principal Investigator: Tsume Mami 地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 病因病態部門, 研究技術員 (70711026)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: ヒストンアセチル化 / BETファミリータンパク質 / 幹細胞 / マウス

Outline of Final Research Achievements

During mammalian early neurogenesis, neural stem/progenitor cells proliferate by self-renewal and differentiate into neurons in a developmental-stage dependent manner, but the roles of histone acetylation in maintenance of stemness and neurogenesis remain unclear. In this study, I analyzed roles of BET family proteins (BET), which specifically bind to lysine residues of acetylated histone H4 through their bromodomains and regulate transcription. I found that BET binding acetylated histones such as H4K5ac and H4K12ac were up-regulated in S-phase of neural progenitor cells specifically. By exploiting a BET inhibitor that blocks the binding to acetylated histones, I also identified that BET is required for the transcription of genes involved in maintenance of stem cells.

Free Research Field

発生生物学