Capicua controls Toll/IL-1 signaling targets independently of RTK regulation

Aikaterini Papagianni, Marta Forés, Wanqing Shao, Shuonan He, Nina Koenecke, María José Andreu, Núria Samper, Ze'ev Paroush, Sergio González-Crespo, Julia Zeitlinger, Gerardo Jiménez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


The HMG-box protein Capicua (Cic) is a conserved transcriptional repressor that functions downstream of receptor tyrosine kinase (RTK) signaling pathways in a relatively simple switch: In the absence of signaling, Cic represses RTK-responsive genes by binding to nearly invariant sites in DNA, whereas activation of RTK signaling down-regulates Cic activity, leading to derepression of its targets. This mechanism controls gene expression in both Drosophila and mammals, but whether Cic can also function via other regulatory mechanisms remains unknown. Here, we characterize an RTK-independent role of Cic in regulating spatially restricted expression of Toll/IL-1 signaling targets in Drosophila embryogenesis. We show that Cic represses those targets by binding to suboptimal DNA sites of lower affinity than its known consensus sites. This binding depends on Dorsal/NF-κB, which translocates into the nucleus upon Toll activation and binds next to the Cic sites. As a result, Cic binds to and represses Toll targets only in regions with nuclear Dorsal. These results reveal a mode of Cic regulation unrelated to the well-established RTK/Cic depression axis and implicate cooperative binding in conjunction with low-affinity binding sites as an important mechanism of enhancer regulation. Given that Cic plays a role in many developmental and pathological processes in mammals, our results raise the possibility that some of these Cic functions are independent of RTK regulation and may depend on cofactor-assisted DNA binding.

Original languageAmerican English
Pages (from-to)1807-1812
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - 20 Feb 2018

Bibliographical note

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© 2018 National Academy of Sciences. All Rights Reserved.


  • ChIP-nexus
  • Dorsal
  • Groucho
  • Low-affinity binding sites
  • Transcriptional repression


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