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Updated: Jul 18, 2026

Computational Analysis of the Caenorhabditis elegans Germline to Study the Distribution of Nuclei, Proteins, and the Cytoskeleton
Published on: April 19, 2018
Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network
W B Derry1, R Bierings, M van Iersel
1Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA. brent.derry@sickkids.ca
Abstract:
Caenorhabditis elegans CEP-1 activates germline apoptosis in response to genotoxic stress, similar to its mammalian counterpart, tumor suppressor p53. In mammals, there are three p53 family members (p53, p63, and p73) that activate and repress many distinct and overlapping sets of genes, revealing a complex transcriptional regulatory network. Because CEP-1 is the sole p53 family member in C. elegans, analysis of this network is greatly simplified in this organism. We found that CEP-1 functions during normal development in the absence of stress to repress many (331) genes and activate only a few (28) genes. In response to genotoxic stress, 1394 genes are activated and 942 are repressed, many of which contain p53-binding sites. Comparison of the CEP-1 transcriptional network with transcriptional targets of the human p53 family reveals considerable overlap between CEP-1-regulated genes and homologues regulated by human p63 and p53, suggesting a composite p53/p63 action for CEP-1. We found that phg-1, the C. elegans Gas1 (growth arrest-specific 1) homologue, is activated by CEP-1 and is a negative regulator of cell proliferation in the germline in response to genotoxic stress. Further, we find that CEP-1 and PHG-1 mediate the decreased developmental rate and embryonic viability of mutations in the clk-2/TEL2 gene, which regulates lifespan and checkpoint responses.
Insights
Caenorhabditis elegans CEP-1, a tumor suppressor, regulates gene expression during development and in response to genotoxic stress. Its network overlaps with human p53/p63, suggesting conserved functions in cell cycle control.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- The tumor suppressor p53 and its family members (p53, p63, p73) regulate complex gene networks in mammals.
- Caenorhabditis elegans possesses a single p53 family member, CEP-1, simplifying the study of p53-mediated transcriptional regulation.
Purpose of the Study:
- To elucidate the transcriptional network regulated by CEP-1 in Caenorhabditis elegans during normal development and in response to genotoxic stress.
- To compare the CEP-1 transcriptional network with human p53 family targets to infer conserved functions.
Main Methods:
- Transcriptome analysis to identify genes regulated by CEP-1 under normal and stress conditions.
- Bioinformatic comparison of CEP-1 target genes with human p53/p63 regulated genes.
- Functional analysis of CEP-1 and its target gene phg-1 in response to genotoxic stress and clk-2/TEL2 mutations.
Main Results:
- CEP-1 represses 331 genes and activates 28 genes during normal development.
- Genotoxic stress leads to CEP-1-mediated activation of 1394 genes and repression of 942 genes.
- CEP-1 regulates genes homologous to those targeted by human p53 and p63, indicating a composite function.
- CEP-1 activates phg-1, a negative regulator of germline proliferation.
- CEP-1 and PHG-1 influence developmental rate and viability in clk-2/TEL2 mutants.
Conclusions:
- CEP-1 functions as a broader transcriptional regulator than previously appreciated, impacting both development and stress response.
- The CEP-1 network shares significant overlap with human p53/p63 targets, suggesting conserved roles in cellular regulation.
- CEP-1 and its target PHG-1 play crucial roles in germline integrity and response to DNA damage, linking to lifespan and checkpoint pathways.
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