短いタンデムリピートは,エウカリオットの遺伝子発現を調整するために転写因子を結合する

Connor A Horton¹, Amr M Alexandari², Michael G B Hayes¹

¹Department of Genetics, Stanford University, Stanford, CA 94305, USA.

Science (New York, N.Y.)

|September 21, 2023

まとめ

短いタンデムリピート (STR) は,直接結合する転写因子 (TF) によって遺伝子発現を変化させる. これらのDNA配列は標的部位でのTF密度を増加させ,新しいシス調節メカニズムを明らかにします.

科学分野:

ゲノミクス
分子生物学
バイオ情報学

背景:

短いタンデムリピート (STR) は,真核細胞のシス調節要素で一般的です.
STRは遺伝子発現に影響することが知られているが,その調節メカニズムは不明である.

研究の目的:

STR が転写を調節するメカニズムを解明する.
転写因子 (TF) -DNA相互作用に対するSTRの影響を調査する.

主な方法:

TF-DNAの親和性や運動性を測定する in vitro 生体物理結合測定法.
TF結合を予測するための統計力学モデリング.
機械学習 (ニューラルネットワーク) で,in vivo占有データで訓練する.

主要な成果:

STRは,TF-DNA結合親和性とオンレートを著しく (最大70倍) 調節する.
STRは,ターゲットサイト近くの弱い好みのマイクロステートを最大化することによって,TF密度を増加させます.
STRは,既知のモチーフの類似性とは無関係に,約90%のTFによって優先的に結合される.

結論:

STRは,TFを特定のゲノム位置にターゲティングするための新しいシス調節メカニズムを提供します.
STRは,TF結合のエネルギーと運動に直接影響し,遺伝子調節に影響を与えます.
計算モデルでは,STRがTF結合に及ぼす影響をin vitroおよびin vivoで正確に予測できます.

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