Enhancers

Abstract

Transcription of eukaryotic genes is an exceedingly sophisticated and complicated process, orchestrated by layers of control mechanisms involving a myriad of transcription factors and DNA control sequences, with both groups subject to multiple modifications. The availability of various recent genomic approaches has provided previously unforeseen opportunities to examine the cis-regulatory landscape of the entire genome, resulting in the identification of a potentially overwhelming number of enhancers and novel enhancer functions. In this review, we focus on the activities of enhancers in metazoans and discuss how they serve to regulate gene expression during early development.

Figure 1

Spatial regulation of goosecoid by short enhancers. (A) Wnt and Nodal signaling areas are shaded in red and in green. The overlapping region (right panel) corresponds to Spemann’s organizer where gsc is activated. (B) Upon Wnt signaling activation, siamois and twin are transcribed via β-catenin and Tcf/Lef. Siamois and Twin homeodomain proteins bind to the proximal enhancer of gsc. A Smad2/4 complex is also formed in the distal enhancer of gsc where nodal signaling is active. These complexes interact synergistically and gsc expression becomes spatially defined in the Spemann’s organizer region.

Figure 2

Arrangement of Even-skipped enhancer modules. (A) The seven stripe of Eve expression in a Drosophila embryo. Eve stripe 2 domain is highlighted. (B) Five different enhancer modules control the expression of Eve. (C) Stripe 2 enhancer module consists of multiple transcriptional factor binding sites. When the Bicoid and Hunchback transcription factors are present, eve stripe 2 is activated. When Giant and Kruppel proteins are available, eve strip 2 element is repressed.

Figure 3

Arrangement of Shh enhancers. CNS specific enhancers and epithelial lining enhancers are shown. Limb enhancer is located approximately 1MB away from the Shh promoter region.