DAF-12 regulates a connected network of genes to ensure robust developmental decisions

Daniel Hochbaum, Yue Zhang, Carsten Stuckenholz, Paul Labhart, Vassili Alexiadis, René Martin, Hans Joachim Knölker, Alfred L. Fisher

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development in unfavorable conditions, and the modulation of adult aging. Despite the biologic importance of DAF-12, target genes for this receptor are largely unknown. To identify DAF-12 targets, we performed chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays. We identified 1,175 genomic regions to be bound in vivo by DAF-12, and these regions are enriched in known DAF-12 binding motifs and act as DAF-12 response elements in transfected cells and in transgenic worms. The DAF-12 target genes near these binding sites include an extensive network of interconnected heterochronic and microRNA genes. We also identify the genes encoding components of the miRISC, which is required for the control of target genes by microRNA, as a target of DAF-12 regulation. During reproductive development, many of these target genes are misregulated in daf-12(0) mutants, but this only infrequently results in developmental phenotypes. In contrast, we and others have found that null daf-12 mutations enhance the phenotypes of many miRISC and heterochronic target genes. We also find that environmental fluctuations significantly strengthen the weak heterochronic phenotypes of null daf-12 alleles. During diapause, DAF-12 represses the expression of many heterochronic and miRISC target genes, and prior work has demonstrated that dauer formation can suppress the heterochronic phenotypes of many of these target genes in post-dauer development. Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions.

Original languageEnglish (US)
Article numbere1002179
JournalPLoS genetics
Volume7
Issue number7
DOIs
StatePublished - Jul 1 2011

Fingerprint

Gene Regulatory Networks
gene
Genes
genes
phenotype
Phenotype
MicroRNAs
microRNA
Gene Components
gene regulatory networks
decision
Chromatin Immunoprecipitation
receptors
Response Elements
Cytoplasmic and Nuclear Receptors
diapause
response elements
chromatin
binding sites
mutation

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Hochbaum, D., Zhang, Y., Stuckenholz, C., Labhart, P., Alexiadis, V., Martin, R., ... Fisher, A. L. (2011). DAF-12 regulates a connected network of genes to ensure robust developmental decisions. PLoS genetics, 7(7), [e1002179]. https://doi.org/10.1371/journal.pgen.1002179

DAF-12 regulates a connected network of genes to ensure robust developmental decisions. / Hochbaum, Daniel; Zhang, Yue; Stuckenholz, Carsten; Labhart, Paul; Alexiadis, Vassili; Martin, René; Knölker, Hans Joachim; Fisher, Alfred L.

In: PLoS genetics, Vol. 7, No. 7, e1002179, 01.07.2011.

Research output: Contribution to journalArticle

Hochbaum, D, Zhang, Y, Stuckenholz, C, Labhart, P, Alexiadis, V, Martin, R, Knölker, HJ & Fisher, AL 2011, 'DAF-12 regulates a connected network of genes to ensure robust developmental decisions', PLoS genetics, vol. 7, no. 7, e1002179. https://doi.org/10.1371/journal.pgen.1002179
Hochbaum D, Zhang Y, Stuckenholz C, Labhart P, Alexiadis V, Martin R et al. DAF-12 regulates a connected network of genes to ensure robust developmental decisions. PLoS genetics. 2011 Jul 1;7(7). e1002179. https://doi.org/10.1371/journal.pgen.1002179
Hochbaum, Daniel ; Zhang, Yue ; Stuckenholz, Carsten ; Labhart, Paul ; Alexiadis, Vassili ; Martin, René ; Knölker, Hans Joachim ; Fisher, Alfred L. / DAF-12 regulates a connected network of genes to ensure robust developmental decisions. In: PLoS genetics. 2011 ; Vol. 7, No. 7.
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