X-chromosome target specificity diverged between dosage compensation mechanisms of two closely related Caenorhabditis species.
X-chromosome target specificity diverged between dosage compensation mechanisms of two closely related Caenorhabditis species.
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DOI：
10.7554/elife.85413
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发表时间：
2023-03-23
期刊：
影响因子：
7.7
通讯作者：
Meyer BJ
中科院分区：
文献类型：
--
作者：
Yang Q;Lo TW;Brejc K;Schartner C;Ralston EJ;Lapidus DM;Meyer BJ
进化的观点增强了我们对生物机制的理解。比较两种线虫的性别决定和X染色体剂量补偿机制发现，控制这两个过程的遗传调控层次是保守的，但控制X表达的特异性凝缩蛋白剂量补偿复合物（DCC）在X染色体上的靶特异性和结合方式存在差异。我们在Cbr DCC招募位点中发现了两个高度富集的基序：13 bp MEX和30 bp MEX II。在一个或两个基序的多个拷贝的内源性招募位点突变MEX或MEX II会减少结合，但仅去除所有基序就会消除体内的结合。因此，DCC与Cbr招募位点的结合似乎是附加的。相比之下，DCC与细胞招募位点的结合是协同的：即使在体内突变一个基序也会消除这种结合。尽管所有的x染色体基序共享CAGGG序列，但它们在其他方面存在分歧，因此来自一个物种的基序不能在另一个物种中发挥作用。在体内和体外均证实了功能分化。Cbr MEX中的单个核苷酸位置可以决定细胞DCC是否结合。DCC靶特异性的快速差异可能是线虫物种之间建立生殖隔离的重要因素，这与果蝇物种之间x染色体剂量补偿的靶特异性守恒以及控制发育过程（如果蝇到小鼠的身体计划规范）的转录因子形成鲜明对比。
An evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode species Caenorhabditis briggsae (Cbr) and Caenorhabditis elegans (Cel) revealed that the genetic regulatory hierarchy controlling both processes is conserved, but the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X expression have diverged. We identified two motifs within Cbr DCC recruitment sites that are highly enriched on X: 13 bp MEX and 30 bp MEX II. Mutating either MEX or MEX II in an endogenous recruitment site with multiple copies of one or both motifs reduced binding, but only removing all motifs eliminated binding in vivo. Hence, DCC binding to Cbr recruitment sites appears additive. In contrast, DCC binding to Cel recruitment sites is synergistic: mutating even one motif in vivo eliminated binding. Although all X-chromosome motifs share the sequence CAGGG, they have otherwise diverged so that a motif from one species cannot function in the other. Functional divergence was demonstrated in vivo and in vitro. A single nucleotide position in Cbr MEX can determine whether Cel DCC binds. This rapid divergence of DCC target specificity could have been an important factor in establishing reproductive isolation between nematode species and contrasts dramatically with the conservation of target specificity for X-chromosome dosage compensation across Drosophila species and for transcription factors controlling developmental processes such as body-plan specification from fruit flies to mice.