性別決定には,SRYとSF1が特定のSox9増強剤に作用し,その作用を相乗的に作用する
Ryohei Sekido1, Robin Lovell-Badge
1Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. rsekido@nimr.mrc.ac.uk
Nature
|May 6, 2008
まとめ
SRYタンパク質は,男性の性別決定の重要な要因であるSox9遺伝子発現を直接調節する. この発見は,哺乳類の丸の発達に不可欠な自己強化経路を明らかにしています.
科学分野:
- 遺伝学 遺伝学とは
- 発達生物学 発達生物学について
- 分子生物学は分子生物学である.
背景:
- Y染色体のSRY遺伝子は,性器の発達を丸に向けることで,男性の性別決定を開始します.
- Sox9はオートソーム性遺伝子で,セルトリ細胞の分化に不可欠であり,XX個体において雄性発育を誘発することができる.
- SRYとSox9規制を結びつける正確なメカニズムは不明のままである.
研究 の 目的:
- 哺乳類の性別決定中にSRYがSox9発現に影響を与える分子メカニズムを解明する.
- Sox9.9の規制におけるSRYとSF1の協力的な役割を調査する.
主な方法:
- クロマチンの免疫プレシピテーション測定は,Sox9増強剤にSRY結合を検出する.
- SRYとSF1のSox9.9に対する機能的影響を評価するための共伝染実験.
- 変異したSRY結合部位を持つ性逆性性腺の分析.
主要な成果:
- SRYは,性腺特異のSox9強化剤内の複数の部位に直接結合する.
- SRYとSF1 (ステロイド生成因子1) は協力してSox9発現を上調する.
- SOX9は,SF1と共に強化剤と結合し,SRYレベルが低下した後も自身の発現を維持し,フィードフォワードループを確立します.
結論:
- SRY,SF1,SOX9を含む新しいフィードフォワード規制ループが,男性の性別決定を制御しています.
- このメカニズムは,SRYがどのようにして細胞の分化を開始し,SOX9がセルトリ細胞の分化を維持するかを説明します.
- 発見は,性決定の進化と性逆転の分子基礎についての洞察を提供します.
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