合作性
转录因子
间充质
Hox基因
同源盒
生物
调节器
遗传学
染色质
DNA
粘蛋白
合作约束
细胞生物学
肢体发育
基因
结合位点
计算生物学
胚胎
作者
Seungsoo Kim,Ekaterina Morgunova,Sahin Naqvi,Maram Bader,Mervenaz Koska,A.N. Popov,Christy Luong,Angela N. Pogson,Peter Claes,Jussi Taipale,Joanna Wysocka
标识
DOI:10.1101/2023.05.29.541540
摘要
Summary 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 it may be common, examples of such cooperativity remain scarce in cellular contexts. Here, we demonstrate how ‘Coordinator’, a long DNA motif comprised of common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines 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, while HD factors stabilize TWIST1 occupancy at Coordinator and titrate it away from HD-independent sites. This cooperativity results in shared regulation of genes involved in cell-type and positional identities, and ultimately shapes facial morphology and evolution.
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