Howard Hughes Medical Institute (HHMI), Janelia Research Campus, Ashburn, VA 20147, USA.
Departamento de Ecología, Genética y Evolución, IEGEBA-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina.
Cell Rep. 2018 Mar 13;22(11):3021-3031. doi: 10.1016/j.celrep.2018.02.073.
Developmental genes can have complex cis-regulatory regions with multiple enhancers. Early work revealed remarkable modularity of enhancers, whereby distinct DNA regions drive gene expression in defined spatiotemporal domains. Nevertheless, a few reports have shown that enhancers function in multiple developmental stages, implying that enhancers can be pleiotropic. Here, we have studied the activity of the enhancers of the shavenbaby gene throughout D. melanogaster development. We found that all seven shavenbaby enhancers drive expression in multiple tissues and developmental stages. We explored how enhancer pleiotropy is encoded in two of these enhancers. In one enhancer, the same transcription factor binding sites contribute to embryonic and pupal expression, revealing site pleiotropy, whereas for a second enhancer, these roles are encoded by distinct sites. Enhancer pleiotropy may be a common feature of cis-regulatory regions of developmental genes, and site pleiotropy may constrain enhancer evolution in some cases.
发育基因可能具有具有多个增强子的复杂顺式调控区。早期的工作揭示了增强子的显著模块性，即不同的 DNA 区域在特定的时空域驱动基因表达。然而，有一些报道表明增强子在多个发育阶段发挥作用，这意味着增强子可以是多效的。在这里，我们研究了 shavenbaby 基因的增强子在 D. melanogaster 发育过程中的活性。我们发现七个 shavenbaby 增强子都在多种组织和发育阶段驱动表达。我们探讨了在这两个增强子中的两个中，增强子的多效性是如何编码的。在一个增强子中，相同的转录因子结合位点有助于胚胎和蛹期的表达，揭示了位点的多效性，而对于第二个增强子，这些作用是由不同的位点编码的。增强子的多效性可能是发育基因顺式调控区的一个共同特征，而在某些情况下，位点的多效性可能会限制增强子的进化。
