Comprehensive Analysis of a cis-Regulatory Region Reveals Pleiotropy in Enhancer Function

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Ella Preger-Ben Noon, Gonzalo Sabarís, Daniela M. Ortiz, Jonathan Sager, Anna Liebowitz, David L. Stern, Nicolás Frankel
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.

Graphical abstract

Teaser

Preger-Ben Noon et al. find that shavenbaby gene enhancers contain regulatory information for driving several expression patterns (i.e., enhancers are pleiotropic) and that, in some cases, the transcription factor binding sites that activate these enhancers are reused during development.


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