Molecular basis for DNA recognition by the maternal pioneer transcription factor FoxH1.
Molecular basis for DNA recognition by the maternal pioneer transcription factor FoxH1.
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DOI：
10.1038/s41467-022-34925-y
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发表时间：
2022-11-26
影响因子：
16.6
通讯作者：
Macias, Maria J.
中科院分区：
文献类型：
--
作者：
Pluta, Radoslaw;Aragon, Eric;Prescott, Nicholas A.;Ruiz, Lidia;Mees, Rebeca A.;Baginski, Blazej;Flood, Julia R.;Martin-Malpartida, Pau;Massague, Joan;David, Yael;Macias, Maria J.
叉头盒H1(Forkhead box H1，FoxH1)是胚胎发育过程中一个重要的母体先锋因子，与特定的含GG/GT的DNA靶序列结合。在这里，我们确定了三个FoxH1蛋白(来自人、青蛙和鱼类)和四个DNA的高分辨率结构，以阐明FoxH1与这些位点结合的方式。我们发现，蛋白质-DNA相互作用延伸到次要和主要DNA沟槽，因此几乎是狐狸家族其他成员的两倍。此外，我们还发现了FoxH1中两个特定的氨基酸变化，它们允许识别GG/GT基序。与FoxH1的先锋因子活性一致，我们发现它对核小体DNA的亲和力甚至高于对线性DNA片段的亲和力。这里报道的结构说明了FoxH1如何与不同的DNA位点结合提供特异性，并避免与其他Fox蛋白质的交叉调节，这些蛋白质也在母体-受精卵转变过程中发挥作用，并选择典型的叉头部位。FoxH1是胚胎发育过程中必不可少的母体先锋因子。在这里，作者提出了几个FoxH1-DNA结构，揭示了FoxH1结合特异性和先锋因子活性的分子基础。
Forkhead box H1 (FoxH1) is an essential maternal pioneer factor during embryonic development that binds to specific GG/GT-containing DNA target sequences. Here we have determined high-resolution structures of three FoxH1 proteins (from human, frog and fish species) and four DNAs to clarify the way in which FoxH1 binds to these sites. We found that the protein-DNA interactions extend to both the minor and major DNA grooves and are thus almost twice as extensive as those of other FOX family members. Moreover, we identified two specific amino acid changes in FoxH1 that allowed the recognition of GG/GT motifs. Consistent with the pioneer factor activity of FoxH1, we found that its affinity for nucleosomal DNA is even higher than for linear DNA fragments. The structures reported herein illustrate how FoxH1 binding to distinct DNA sites provides specificity and avoids cross-regulation by other FOX proteins that also operate during the maternal-zygotic transition and select canonical forkhead sites. FoxH1 is an essential maternal pioneer factor during embryonic development. Here, the authors present several FoxH1—DNA structures that reveal the molecular basis for FoxH1 binding specificity and pioneer factor activity.
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