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The Grainyhead/LSF transcription factor GRH-1 is rhythmically required for molting

View ORCID ProfileMilou W.M. Meeuse, View ORCID ProfileYannick P. Hauser, View ORCID ProfileSmita Nahar, View ORCID ProfileKathrin Braun, View ORCID ProfileHelge Großhans
doi: https://doi.org/10.1101/2022.03.01.482504
Milou W.M. Meeuse
1Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, CH-4058 Basel
2University of Basel, Petersplatz 1, CH-4001 Basel
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  • ORCID record for Milou W.M. Meeuse
Yannick P. Hauser
1Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, CH-4058 Basel
2University of Basel, Petersplatz 1, CH-4001 Basel
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Smita Nahar
1Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, CH-4058 Basel
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Kathrin Braun
1Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, CH-4058 Basel
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Helge Großhans
1Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, CH-4058 Basel
2University of Basel, Petersplatz 1, CH-4001 Basel
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  • For correspondence: helge.grosshans@fmi.ch
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Abstract

Molting, that is, the synthesis and shedding of a cuticular exoskeleton, is a defining characteristic of ecdysozoa. In nematodes such as C. elegans, molts rhythmically terminate each of four larval stages. The molting cycle is tightly coupled to the rhythmic accumulation of thousands of transcripts. Here, using chromatin immunoprecipitation coupled to sequencing (ChIP-seq) and quantitative reporter assays, we show that these dynamic gene expression patterns rely on rhythmic transcription. To gain insight into the relevant gene regulatory networks (GRNs), we performed an RNAi-based screen for transcription factors required for molting to identify potential components of a molting clock. We find that depletion of GRH-1, BLMP-1, NHR-23, NHR-25, MYRF-1 or BED-3 impairs progression through the molting cycle. We characterize GRH-1, a Grainyhead/LSF transcription factor whose orthologues in other animals are key epithelial cell fate regulators. We show that GRH-1 depletion causes a dose-dependent extension of molt duration, defects in cuticle formation and shedding, and larval death. Coincident with its rhythmic accumulation, GRH-1 is required repetitively for each molt, during specific time windows preceding lethargus. These findings are consistent with a function of GRH-1 in a molting cycle GRN. As its mammalian orthologues, as well as those of BLMP-1 and NHR-23, have been implicated in rhythmic homeostatic skin regeneration in mouse, the mechanisms underlying rhythmic C. elegans molting may apply beyond nematodes.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • New Figures 1, S1-S2 revealing transcriptional control of oscillations

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 16, 2022.
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The Grainyhead/LSF transcription factor GRH-1 is rhythmically required for molting
Milou W.M. Meeuse, Yannick P. Hauser, Smita Nahar, Kathrin Braun, Helge Großhans
bioRxiv 2022.03.01.482504; doi: https://doi.org/10.1101/2022.03.01.482504
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The Grainyhead/LSF transcription factor GRH-1 is rhythmically required for molting
Milou W.M. Meeuse, Yannick P. Hauser, Smita Nahar, Kathrin Braun, Helge Großhans
bioRxiv 2022.03.01.482504; doi: https://doi.org/10.1101/2022.03.01.482504

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