Author:
Kuang Yi,Pyo Anna,Eafergan Natanel,Cain Brittany,Gutzwiller Lisa M.,Axelrod Ofri,Gagliani Ellen K.,Weirauch Matthew T.,Kopan Raphael,Kovall Rhett A.,Sprinzak David,Gebelein Brian
Abstract
AbstractNotch signaling controls many developmental processes by regulating gene expression. Notch-dependent enhancers recruit activation complexes consisting of the Notch intracellular domain, theCbf/Su(H)/Lag1 (CSL) transcription factor (TF), and the Mastermind co-factor via two types of DNA sites: monomeric CSL sites and cooperative dimer sites calledSu(H)pairedsites (SPS). Intriguingly, the CSL TF can also bind co-repressors to negatively regulate transcription via these same sites. Here, we tested how enhancers with monomeric CSL sites versus dimeric SPSs bindDrosophilaSu(H) complexesin vitroand mediate transcriptional outcomesin vivo. Our findings reveal that while the Su(H)/Hairless co-repressor complex similarly binds SPS and CSL sites in an additive manner, the Notch activation complex binds SPSs, but not CSL sites, in a cooperative manner. Moreover, transgenic reporters with SPSs mediate stronger, more consistent transcription and are more resistant to increased Hairless co-repressor expression compared to reporters with the same number of CSL sites. These findings support a model in which SPS containing enhancers preferentially recruit cooperative Notch activation complexes over Hairless repression complexes to ensure consistent target gene activation.
Publisher
Cold Spring Harbor Laboratory