Δημοσίευση

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

ΤίτλοςCapicua controls Toll/IL-1 signaling targets independently of RTK regulation.
Publication TypeJournal Article
Year of Publication2018
AuthorsPapagianni, A., Forés M., Shao W., He S., Koenecke N., Andreu M. José, Samper N., Paroush Z'ev., González-Crespo S., Zeitlinger J., & Jiménez G.
JournalProc Natl Acad Sci U S A
Volume115
Issue8
Pagination1807-1812
Date Published2018 02 20
ISSN1091-6490
Λέξεις κλειδιάAnimals, Basic Helix-Loop-Helix Transcription Factors, Cell Nucleus, Drosophila, Drosophila Proteins, Female, Gene Expression Regulation, Developmental, HMGB Proteins, Male, Nuclear Proteins, Phosphoproteins, Promoter Regions, Genetic, Receptor Protein-Tyrosine Kinases, Repressor Proteins, Signal Transduction, Toll-Like Receptors, Transcription Factors
Abstract

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 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 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.

DOI10.1073/pnas.1713930115
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID29432195
PubMed Central IDPMC5828586

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