Tackling the global regulation of Hox clusters with molecular evolutionary and epigenomic approaches

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03269
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: National Institute of Genetics
• Principal Investigator: Kuraku Shigehiro 国立遺伝学研究所, ゲノム・進化研究系, 教授 (40391940)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Hox / 軟骨魚類 / 円口類 / ゲノムアセンブリ / エピゲノム / 遺伝子発現制御

Outline of Final Research Achievements

We conducted a comparative analysis on the mechanisms of the regulation of Hox gene cluster, based on epigenome analysis techniques and molecular evolutionary approaches. While more detailed comparisons covering a broader range of species and developmental stages are anticipated, this project revealed that the TAD structure mediated by CTCF is commonly shared by a wide range of vertebrates as well as tetrapods. Also, as an example of deviation from this typical pattern, we unveiled that the structural constraints of the HoxC cluster are significantly relaxed in cartilaginous fishes including sharks and rays, leading to a degenerated gene repertoire and TAD structure. Additionally, this project enabled the establishment of sustainable cell culture systems and the characterization of shark sex chromosomes.

Free Research Field

分子進化学、発生生物学、ゲノム情報学

Academic Significance and Societal Importance of the Research Achievements

我々ヒトの頭尾軸に沿った体づくりを制御しているHox遺伝子群は、A-Dのグループに分けられ4本の染色体上にそれぞれ約10個の遺伝子が近接して存在している。それぞれのグループはその並びに従って調和をもって機能するが、その調和をもたらすメカニズムが、我々ヒトとサメ等の軟骨魚類とが分岐したおよそ4億年前の時点ですでに成立していた可能性が示された。この成果は、生物の進化の歴史に基づいて現存の生物のDNA配列情報を種間で比較し、さらに、その情報が発現されるしくみを組織や細胞のレベルで調べる実験手法を駆使して得られたものである。