Cell fate determination through transcriptional activation by BET family proteins in preimplantation embryos

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15738
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Osama Woman's and Children's Hospital
• Principal Investigator: Mami Tsume 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): 2018-04-01 – 2022-03-31
• Keywords: マウス / 着床前胚 / エピブラスト / BETファミリータンパク質 / Brd4 / Brd2 / STAT3

Outline of Final Research Achievements

During mammalian preimplantation development, as the fertilized egg develops and differentiates, three cell lineages become specified: trophectoderm, epiblast, and primitive endoderm. The formation of the three lineages is primarily controlled by expression of the lineage-specific transcription factors. In this research, we focused on the function of transcriptional activation of BET family proteins through the binding of BET bromodomains to acetylated histone and examined the function of the BET proteins during the cell fate specification in mouse preimplantation development. The results indicate that BET proteins are essential to the specification and maintenance of the epiblast lineage by activating lineage-specific core transcription factors through partly association with the STAT3-dependent pathway during mouse preimplantation development. Furthermore, among BET proteins, BRD4 plays a central role and BRD2 a complementary role in the specification of epiblast lineages.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

BETの発生過程における機能については、ノックアウトマウスの解析が行われていたものの、着床前胚での細胞運命決定における機能については不明確であり、ユビキタスに発現するBETがSTAT3依存性の経路を部分的に介してエピブラスト系譜特異的に働いていることは本研究課題で初めて明らかにされた。BETファミリーは神経組織など他の組織でもユビキタスに発現することから、得られた知見は、他の臓器や組織形成での細胞分化における転写制御機構についても普遍化できることが期待される。