PDF(Pubmed)
Abstract：
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. Although in vitro studies 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.
摘要：
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可能很常见，这种合作的例子在细胞环境中仍然很少。这里,我们演示了“协调员，“由许多基本螺旋-环-螺旋（bHLH）和同源结构域（HD）TF结合的共同基序组成的长DNA基序，独特地定义了胚胎面部和肢体间充质的调节区域。协调员指导bHLH家族间充质调节因子TWIST1和一组与面部和肢体区域身份相关的HD因子之间的合作和选择性结合。TWIST1是HD结合和在协调位点开放染色质所必需的，而HD因子在协调员处稳定TWIST1占用率，并将其从独立于HD的站点滴定。这种协同作用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。
