Evolutionary emergence of Hairless as a novel component of the Notch signaling pathway
- University of California, San Diego, United States
- Center for Genomic Regulation, Spain
Abstract
Suppressor of Hairless [Su(H)], the transcription factor at the end of the Notch pathway in Drosophila, utilizes the Hairless protein to recruit two co-repressors, Groucho (Gro) and C-terminal Binding Protein (CtBP), indirectly. Hairless is present only in the Pancrustacea, raising the question of how Su(H) in other protostomes gains repressive function. We show that Su(H) from a wide array of arthropods, molluscs, and annelids includes motifs that directly bind Gro and CtBP; thus, direct co-repressor recruitment is ancestral in the protostomes. How did Hairless come to replace this ancestral paradigm? Our discovery of a protein (S-CAP) in Myriapods and Chelicerates that contains a motif similar to the Su(H)-binding domain in Hairless has revealed a likely evolutionary connection between Hairless and Metastasis-associated (MTA) protein, a component of the NuRD complex. Sequence comparison and widely conserved microsynteny suggest that S-CAP and Hairless arose from a tandem duplication of an ancestral MTA gene.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institute of General Medical Sciences (R01GM046993)
- James W Posakony
National Institute of General Medical Sciences (R01GM120377)
- James W Posakony
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Miller et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Evolutionary emergence of Hairless as a novel component of the Notch signaling pathway
eLife 8:e48115.
https://doi.org/10.7554/eLife.48115
