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2021 Fiscal Year Final Research Report

Landscape of enhancer for nephric tubule regeneration

Research Project

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Project/Area Number 19K06672
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionYamagata University

Principal Investigator

Ochi Haruki  山形大学, 医学部, 准教授 (00505787)

Project Period (FY) 2019-04-01 – 2022-03-31
Keywords再生エンハンサー / 網羅的オープンクロマチン解析 / 腎再生 / 転写因子 / ゲノム / シス調節配列 / アフリカツメガエル / ネッタイツメガエル
Outline of Final Research Achievements

We first collected proximal and intermediate tubules from Xenopus Pax8:GFP positive uninjured (day 0), regenerating (day 2), and regenerated (day 5) conditions for ATAC-seq and H3K27ac ChIP-seq, and uninjured (day 0), uninjured (day 2), and regenerating (day 2) conditions for RNA-seq. We then obtained putative enhancers of regeneration based on these data sets. In vivo enhancer activities for putative enhancers were tested using Xenopus transgenic system and confirmed that putative enhancers were activated after the injury of nephric tubules. Then, we applied the HOMER tools to identify drivers of the regeneration enhancers. We found a robust enrichment of Pbx, Tead, Klf motifs in regenerating specific open chromatin elements. Transcriptional activities were tested using luciferase reporter system, and Klf functions as an activator for these elements. These results suggest that the transcriptional activator of Klfs is one of the regulators for nephric tubules regeneration enhancers.

Free Research Field

遺伝子発現制御

Academic Significance and Societal Importance of the Research Achievements

組織・器官の再生では発生過程で使われた遺伝子が再び発現することが知られている。しかしながら、これら発生制御遺伝子の再発現を担うエンハンサーがいずれの転写因子により活性化されるのか全ゲノムレベルでその機能を捉える研究は殆どなされていなかった。本研究は哺乳類と同様に損傷後の残存している細胞から尿細管を再生する両生類をモデルとしてその問の解決に挑み、腎尿細管再生における全ゲノムレベルでの再生エンハンサーと活性化因子を明らかにした。これらエンハンサーや活性化メカニズムは哺乳類においても進化的に保存されていると予想され、将来の再生医療技術の発展に繋がる点において社会的意義が高い。

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Published: 2023-01-30  

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