Regulatory elements: Putting enhancers into context

· by Xin He · Read in about 1 min · (106 words) ·

Regulatory elements: Putting enhancers into context

Principle of suboptimization

The enhancer consists of low-affinity TF binding sites in a suboptimal syntax, in terms of flanking nucleotides and spacing between the sites. Optimizing the TF binding affinities can lead to ectopic expression.

Experiment

In sea squirt, 15 synthetic enhancers consisting of 2 ETS binding sites and a ZicL binding site. Only 2 show activities. Further manipulation confirm key roles for binding site orientation, spacing and flanking nucleotides.

Lesson

Activity of enhancers depend on binding affinities of sites, flanking bases, site arrangement (orientation and spacing). For a particular enhancer, he desired activity level is not necessarily the strongest.