Li Lily, Wunderlich Zeba
Department of Developmental and Cell Biology, University of California, IrvineIrvine, CA, United States.
Front Genet. 2017 May 23;8:63. doi: 10.3389/fgene.2017.00063. eCollection 2017.
Enhancers drive the gene expression patterns required for virtually every process in metazoans. We propose that enhancer length and transcription factor (TF) binding site composition-the number and identity of TF binding sites-reflect the complexity of the enhancer's regulatory task. In development, we define regulatory task complexity as the number of fates specified in a set of cells at once. We hypothesize that enhancers with more complex regulatory tasks will be longer, with more, but less specific, TF binding sites. Larger numbers of binding sites can be arranged in more ways, allowing enhancers to drive many distinct expression patterns, and therefore cell fates, using a finite number of TF inputs. We compare ~100 enhancers patterning the more complex anterior-posterior (AP) axis and the simpler dorsal-ventral (DV) axis in and find that the AP enhancers are longer with more, but less specific binding sites than the (DV) enhancers. Using a set of ~3,500 enhancers, we find enhancer length and TF binding site number again increase with increasing regulatory task complexity. Therefore, to be broadly applicable, computational tools to study enhancers must account for differences in regulatory task.
增强子驱动后生动物几乎每个过程所需的基因表达模式。我们提出，增强子长度和转录因子（TF）结合位点组成——TF结合位点的数量和特性——反映了增强子调控任务的复杂性。在发育过程中，我们将调控任务复杂性定义为一组细胞中同时指定的命运数量。我们假设，具有更复杂调控任务的增强子会更长，具有更多但特异性更低的TF结合位点。大量的结合位点可以以更多方式排列，使增强子能够利用有限数量的TF输入驱动许多不同的表达模式，进而决定细胞命运。我们比较了约100个在[具体生物]中调控更复杂的前后轴（AP）和较简单的背腹轴（DV）的增强子，发现AP增强子比DV增强子更长，具有更多但特异性更低的结合位点。使用一组约3500个增强子，我们再次发现增强子长度和TF结合位点数量随着调控任务复杂性的增加而增加。因此，为了广泛适用，研究增强子的计算工具必须考虑调控任务的差异。
