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Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans
Open accessPreprint — published as 10.7554/elife.84355.3 · Paper page
Abstract
Abstract A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types in the developing Caenorhabditis elegans somatic gonad that derive from equipotent progenitors, but exhibit distinct cell behaviors: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We show that the fates of these cells post-specification are more plastic than previously appreciated and that levels of NHR-67 are important for discriminating between invasive and proliferative behavior. Transcription of nhr-67 is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. By screening for proteins that colocalize with NHR-67 punctae, we identified new regulators of uterine cell fate maintenance: homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1. We propose a model in which association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo.
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Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Metadata
- Authors
- Medwig-Kinney, T. N., Kinney, B. A., Martinez, M. A. Q., Yee, C., Sirota, S. S., Mullarkey, A. A., Somineni, N., Hippler, J., Zhang, W., Shen, K., Hammell, C. M., Pani, A. M., & Matus, D. Q.
- Affiliations
- Stony Brook University (US)
- Cold Spring Harbor Laboratory (US)
- Howard Hughes Medical Institute (US)
- University of Virginia (US)
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-09-26
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W4387048210
- Cited by
- 0
- References
- 2
- Type
- posted content
- Language
- en
- Open access
- gold
- doi.org
- Locations
- eLife (acceptedVersion, cc-by)
- Funders
- National Institutes of Health (R01GM121597, F31HD100091, F30CA257383, R01GM117406, R35GM142880)
- Damon Runyon Cancer Research Foundation (DRR-47-17)
- Stony Brook University (Presidential Critical Research Funds)
- Human Frontier Science Program (LTF000127/2016-L)
- Howard Hughes Medical Institute (Investigator)
- National Science Foundation (2217560)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Groucho, POP-1, anchor cell, basement membrane invasion, corepressors, nuclear compartmentalization, cell fate maintenance, Caenorhabditis elegans
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