DNA-guided transcription factor cooperativity shapes face and limb mesenchyme.
DNA-guided transcription factor cooperativity shapes face and limb mesenchyme.
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DNA 引导的转录因子协同作用塑造面部和肢体间质。
DOI：
10.1101/2023.05.29.541540
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Wysocka,Joanna
中科院分区：
文献类型：
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作者：
Kim,Seungsoo;Morgunova,Ekaterina;Naqvi,Sahin;Bader,Maram;Koska,Mervenaz;Popov,Alexander;Luong,Christy;Pogson,Angela;Claes,Peter;Taipale,Jussi;Wysocka,Joanna
转录因子（TF）可以定义不同的细胞身份，尽管几乎相同的DNA结合特异性。实现调节特异性的一种机制是DNA引导的TF协同性。尽管体外研究表明这种协同性可能很常见，但在细胞环境中这种协同性的例子仍然很少。在这里，我们展示了如何“协调员”，一个长的DNA基序组成的共同的基序结合许多基本的螺旋-环-螺旋（bHLH）和同源结构域（HD）TF，唯一定义的调控区域的胚胎脸和四肢间充质。协调员指导bHLH家族间充质调节因子TWIST 1和与面部和肢体区域身份相关的HD因子集合之间的合作和选择性结合。TWIST 1是HD结合和协调位点处开放染色质所必需的，而HD因子稳定了协调位点处的TWIST 1占用，并将其滴定远离HD非依赖性位点。这种协同性导致参与细胞类型和位置身份的基因的共同调节，并最终塑造面部形态和进化。
Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Althoughin vitrostudies suggest that it may be common, examples of such cooperativity remain scarce in cellular contexts. Here, we demonstrate how "Coordinator," a long DNA motif composed of common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines the regulatory regions of embryonic face and limb mesenchyme. Coordinator guides cooperative and selective binding between the bHLH family mesenchymal regulator TWIST1 and a collective of HD factors associated with regional identities in the face and limb. TWIST1 is required for HD binding and open chromatin at Coordinator sites, whereas HD factors stabilize TWIST1 occupancy at Coordinator and titrate it away from HD-independent sites. This cooperativity results in the shared regulation of genes involved in cell-type and positional identities and ultimately shapes facial morphology and evolution.