title: The GATA transcription factor/MTA-1 homolog egr-1 promotes longevity and stress resistance in Caenorhabditis elegans.
abstract: Aging is associated with a large number of both phenotypic and molecular changes, but for most of these, it is not known whether these changes are detrimental, neutral, or protective. We have identified a conserved Caenorhabditis elegans GATA transcription factor/MTA-1 homolog egr-1 (lin-40) that extends lifespan and promotes resistance to heat and UV stress when overexpressed. Expression of egr-1 increases with age, suggesting that it may promote survival during normal aging. This increase in expression is dependent on the presence of the germline, raising the possibility that egr-1 expression is regulated by signals from the germline. In addition, loss of egr-1 suppresses the long lifespan of insulin receptor daf-2 mutants. The DAF-16 FOXO transcription factor is required for the increased stress resistance of egr-1 overexpression mutants, and egr-1 is necessary for the proper regulation of sod-3 (a reporter for DAF-16 activity). These results indicate that egr-1 acts within the insulin signaling pathway. egr-1 can also activate the expression of its paralog egl-27, another factor known to extend lifespan and increase stress resistance, suggesting that the two genes act in a common program to promote survival. These results identify egr-1 as part of a longevity-promoting circuit that changes with age in a manner that is beneficial for the lifespan of the organism.
authors.affiliation: Department of Genetics, Stanford University Medical Center, Stanford, CA, 94305, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Zimmerman
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000107:Acetylation / Q000528:radiation effects; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000737:chemistry*; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D005854:Germ Cells / Q000378:metabolism / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D006358:Hot Temperature; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000528:radiation effects; D018384:Oxidative Stress / Q000528:radiation effects; D034622:RNA Interference / Q000528:radiation effects; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D013312:Stress, Physiological / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D029742:Caenorhabditis elegans Proteins; C552215:EGRH-1 protein, C elegans; D050980:GATA Transcription Factors; D006657:Histones; D007328:Insulin
keywords: Caenorhabditis elegans; GATA; NuRD; aging; gene regulation; insulin signaling; stress