Department of Molecular and Cell Biology, University of California-Berkeley, CA 94720, USA.
Curr Biol. 2010 Sep 14;20(17):R754-63. doi: 10.1016/j.cub.2010.06.070.
Regulatory DNAs serve as templates to bring weakly interacting transcription factors into close proximity so they can work synergistically to switch genes on and off in time and space. Most of these regulatory DNAs are enhancers that can work over long distances--a million base pairs or more in mammals--to control gene expression. Critical enhancers are sometimes even found within the introns of neighboring genes. This review summarizes well-defined examples of enhancers controlling key processes in animal development. Potential mechanisms of transcriptional synergy are discussed with regard to enhancer structure and contemporary ChIP-sequencing assays, whereby just a small fraction of the observed binding sites represent bona fide regulatory DNAs. Finally, there is a discussion of how enhancer evolution can produce novelty in animal morphology and of the prospects for reconstructing transitions in animal evolution by introducing derived enhancers in basal ancestors.
调控 DNA 作为模板，将弱相互作用的转录因子拉近，使它们能够协同工作，在时间和空间上适时地开启和关闭基因。这些调控 DNA 大多数是增强子，可以在远距离（哺乳动物中可达 100 万个碱基对或更长）起作用，以控制基因表达。关键增强子有时甚至存在于相邻基因的内含子中。本综述总结了增强子控制动物发育关键过程的明确定义的例子。讨论了转录协同作用的潜在机制，包括增强子结构和当代 ChIP-seq 检测，其中只有一小部分观察到的结合位点代表真正的调控 DNA。最后，还讨论了增强子进化如何产生动物形态的新颖性，以及通过在基础祖先中引入衍生增强子来重建动物进化的过渡的前景。
