Cross-species study of unsolved structure and function of human ultraconserved elements

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Evolutionary biology
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: Takano Toshiyuki 京都工芸繊維大学, 応用生物学系, 教授 (90202150)
• Co-Investigator(Kenkyū-buntansha): 都丸 雅敏 京都工芸繊維大学, 応用生物学系, 助教 (70324720)
• Research Collaborator: Ohsako Takashi ; Timothy Karr
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 超保存配列 / ショウジョウバエ / 遺伝子発現制御 / エンハンサー / 生物種横断研究

Outline of Final Research Achievements

Comparative genomics has identified a large number of non-coding segments that have been highly conserved over hundreds of millions of years of vertebrate evolution (so-called ultra-conserved elements, UCE). To examine their functions in vivo, we generated over 400 Drosophila transgenic lines, each containing a unique human non-coding ultra-conserved element inserted upstream of a core promoter fused to a GAL4 gene, and then assessed their enhancer activities. We observed reporter GFP expression in one or more tissues of larvae or adults in all tested elements, implying that human ultra-conserved elements can function as enhancer in Drosophila. Most of the elements studied induced GFP expression in larval CNS, whereas no UCE induced expression in adult testis. The findings suggest that the transcriptional environment of testis cells significantly differs between human and fly. Alternatively, but not mutually exclusive, the UCEs may function specifically in brain.

Free Research Field

ゲノム進化学

Academic Significance and Societal Importance of the Research Achievements

超保存配列は、遺伝子をコードする領域だけでなく、非コード領域にも存在し、遺伝子発現の制御に関わることが示唆されている。しかし、実際にマウス等をつかってエンハンサー活性が実証されたのは約半数にとどまる。本研究によって、はじめて超保存配列のそのすべてがエンハンサー活性を有することが明らかになった。また、エンハンサー活性の組織特異性は細胞内環境の保存性の違いを示唆する。脳と違って、精巣の発現制御の環境は速く進化しているのかもしれない。