RRC ID 53417
Author Demoinet E, Li S, Roy R.
Title AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans.
Journal Proc Natl Acad Sci U S A
Abstract Life history events, such as traumatic stress, illness, or starvation, can influence us through molecular changes that are recorded in a pattern of characteristic chromatin modifications. These modifications are often associated with adaptive adjustments in gene expression that can persist throughout the lifetime of the organism, or even span multiple generations. Although these adaptations may confer some selective advantage, if they are not appropriately regulated they can also be maladaptive in a context-dependent manner. We show here that during periods of acute starvation in Caenorhabditis elegans larvae, the master metabolic regulator AMP-activated protein kinase (AMPK) plays a critical role in blocking modifications to the chromatin landscape. This ensures that gene expression remains inactive in the germ-line precursors during adverse conditions. In its absence, critical chromatin modifications occur in the primordial germ cells (PGCs) of emergent starved L1 larvae that correlate with compromised reproductive fitness of the generation that experienced the stress, but also in the subsequent generations that never experienced the initial event. Our findings suggest that AMPK regulates the activity of the chromatin modifying COMPASS complex (complex proteins associated with Set1) to ensure that chromatin marks are not established until nutrient/energy contingencies are satisfied. Our study provides molecular insight that links metabolic adaptation to transgenerational epigenetic modification in response to acute periods of starvation.
Volume 114(13)
Pages E2689-E2698
Published 2017-3-28
DOI 10.1073/pnas.1616171114
PII 1616171114
PMID 28289190
PMC PMC5380097
MeSH AMP-Activated Protein Kinases / genetics AMP-Activated Protein Kinases / metabolism AMP-Activated Protein Kinases / physiology* Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Diapause / genetics Epigenesis, Genetic PTEN Phosphohydrolase / genetics PTEN Phosphohydrolase / metabolism PTEN Phosphohydrolase / physiology Reproduction / genetics Starvation Stress, Physiological*
IF 9.412
Times Cited 18
C.elegans tm1944 tm1231 tm1941