Evolutionary emergence of Hairless as a novel component of the Notch signaling pathway.

Steven W Miller,Artem Movsesyan,Rosa Fernández,James W Posakony,Sui Zhang

doi:10.7554/elife.48115

Steven W Miller, Artem Movsesyan + Show 3 more

Open Access

https://doi.org/10.7554/elife.48115

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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.

Highlights

A very common paradigm in the regulation of animal development is that DNA-binding transcriptional repressors bear defined amino acid sequence motifs that permit them to recruit, by direct interaction, one or more common co-repressor proteins that are responsible for conferring repressive activity
We show that Su(H) in a broad range of protostomes, including arthropods, molluscs, and annelids, bears both a short linear motif that mediates binding of C-terminal Binding Protein (CtBP) and a novel motif for direct recruitment of Gro
What can we learn about the evolutionary history of Hairless? While Hairless itself is found only in the Pancrustacea, we show that the genomes of Myriapods and Chelicerates encode a protein with clear sequence and functional similarities to Hairless. These proteins include a motif that strongly resembles the Su(H)-binding domain of Hairless, and we demonstrate that this motif from the house spider Parasteatoda tepidariorum does bind Su(H)

Summary

Introduction

A very common paradigm in the regulation of animal development is that DNA-binding transcriptional repressors bear defined amino acid sequence motifs that permit them to recruit, by direct interaction, one or more common co-repressor proteins that are responsible for conferring repressive activity. Two such universal co-repressors are Groucho (Gro) and C-terminal Binding Protein (CtBP). Resembles the Su(H)-binding domain of Hairless, and we demonstrate that this motif from the house spider Parasteatoda tepidariorum does bind Su(H) These Myriapod and Chelicerate proteins include one or more canonical motifs for recruitment of CtBP. We believe that our study has yielded valuable insight into both the emergence of an evolutionary novelty and its replacement of an ancestral paradigm

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Materials and methods

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