美国斯坦福大学Joanna Wysocka小组发现，DNA引导的转录因子协同作用塑造面部和肢体间充质。相关论文发表在2023年1月22日出版的《细胞》杂志上。

研究人员展示了“协调者”是如何独特地定义胚胎面部和肢体间质的调控区域的，这是由许多基本螺旋-环-螺旋（bHLH）和同源结构域（HD）转录因子（TF）结合的共同基序组成的长DNA基序。协调者引导bHLH家族间充质调节因子TWIST1，与一系列与面部和四肢区域特征相关的HD因子之间的合作性和选择性结合。

TWIST1是HD结合和在协调者位点开放染色质所必需的，而HD因子则稳定TWIST1在协调者位点的占有率，并将其从独立于HD的位点滴定。这种合作性导致了对细胞类型和位置特征相关基因的共同调控，并最终塑造了面部形态和演变。

据介绍，尽管DNA结合特异性几乎相同，TF仍能确定不同的细胞特性。实现调控特异性的一种机制是DNA引导的TF协同作用。虽然体外研究表明这种机制很常见，但在细胞环境中这种合作性的例子仍然很少。

附：英文原文

Title: DNA-guided transcription factor cooperativity shapes face and limb mesenchyme

Author: Seungsoo Kim, Ekaterina Morgunova, Sahin Naqvi, Seppe Goovaerts, Maram Bader, Mervenaz Koska, Alexander Popov, Christy Luong, Angela Pogson, Tomek Swigut, Peter Claes, Jussi Taipale, Joanna Wysocka

Issue&Volume: 2023-01-22

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.

DOI: 10.1016/j.cell.2023.12.032

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01438-1