Enhancer divergence and cis-regulatory evolution in the human and chimp neural crest.
Enhancer divergence and cis-regulatory evolution in the human and chimp neural crest.
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DOI：
10.1016/j.cell.2015.08.036
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发表时间：
2015-09-24
期刊：
影响因子：
64.5
通讯作者：
Wysocka J
中科院分区：
文献类型：
--
作者：
Prescott SL;Srinivasan R;Marchetto MC;Grishina I;Narvaiza I;Selleri L;Gage FH;Swigut T;Wysocka J
顺式调控变化在形态分化中起着核心作用，然而人类特征出现的调控原理仍然知之甚少。在这里，我们使用来自人类和黑猩猩颅神经嵴细胞的表观基因组分析来系统和定量地注释颅面顺式调节景观的差异。表观基因组差异可归因于同源增强子上TF基序的遗传变异，其中一个新的基序最能预测活性偏差。我们探索了这种顺式调控变化的特性，揭示了特定逆转录因子的作用，揭示了与人类面部变异相关的基因附近广泛的物种偏向增强子簇，并证明顺式调控差异与关键神经嵴调控因子的定量表达差异有关。我们的工作为未来的进化研究提供了丰富的候选者，并证明了“细胞人类学”的价值，这是一种使用体外来源的胚胎细胞类型来阐明高等灵长类动物形态变异的基本和进化机制的策略。
Cis-regulatory changes play a central role in morphological divergence, yet the regulatory principles underlying emergence of human traits remain poorly understood. Here we use epigenomic profiling from human and chimpanzee cranial neural crest cells to systematically and quantitatively annotate divergence of craniofacial cis-regulatory landscapes. Epigenomic divergence is attributable to genetic variation within TF motifs at orthologous enhancers, with a novel motif being most predictive of activity biases. We explore properties of this cis-regulatory change, revealing the role of particular retroelements, uncovering broad clusters of species-biased enhancers near genes associated with human facial variation, and demonstrating that cis-regulatory divergence is linked to quantitative expression differences of crucial neural crest regulators. Our work provides a wealth of candidates for future evolutionary studies and demonstrates the value of ‘cellular anthropology’, a strategy of using in vitro-derived embryonic cell types to elucidate both fundamental and evolving mechanisms underlying morphological variation in higher primates.