単一の嗅覚受容体発現のための手段として,エンハンサー相互作用ネットワーク

Eirene Markenscoff-Papadimitriou¹, William E Allen², Bradley M Colquitt¹

¹Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.

Cell

|November 24, 2014

まとめ

研究者らは,複数の嗅覚受容体 (OR) 増強剤が相互作用して,単一のOR遺伝子活性化を保証することを発見しました. この複雑な相互作用が,嗅覚受容体遺伝子の正確で強固な発現を説明しています.

科学分野:

遺伝学遺伝学とは
分子生物学は分子生物学である.
神経科学は神経科学である.

背景:

嗅覚受容体 (OR) 遺伝子発現は嗅覚に不可欠ですが,何千ものORアレルのうちの1つの正確な転写活性化は不明のままです.
OR遺伝子調節を理解することは,嗅覚系機能の解読に不可欠です.

研究の目的:

新種の嗅覚受容体強化剤を特定し,特徴づけること.
嗅覚神経細胞におけるこれらの増強剤のインビボ活性と調節機構を調査する.
OR遺伝子活性化における特定の転写因子の役割を明らかにする.

主な方法:

エピジェネティックシグネチャーを用いて,候補OR強化剤の識別.
嗅覚ニューロンにおける強化剤の活性に関するインビボ研究.
染色体間相互作用と転写因子結合パターンの分析.
転写因子Bptf.f.の役割を評価するための機能検査.

主要な成果:

大量の推定OR増強剤が特定され,その多くは独特の表遺伝子記号を示しています.
これらの増強剤は,OR転写と相関する広範な染色体間相互作用に関与します.
転写因子Bptfは,強化剤の相互作用とOR転写の両方の主要な促進剤として特定されました.
染色体間相互作用の障害は,異変性,多遺伝子性OR発現につながった.

結論:

嗅覚受容体の転写は,相互作用する強化剤の複雑なネットワークによって調節され,しばしば染色体全体に及ぶ.
Bptfのような要因によって促進される複数の強化剤の協調的な作用は,個々のOR遺伝子の単一で堅牢な発現を保証します.
単一のOR場所における多数の強化剤のストキャスティック収束は,嗅覚受容体遺伝子活性化の特異性と信頼性を裏付けている可能性が高い.

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