Surviving Starvation: AMPK Protects Germ Cell Integrity by Targeting Multiple Epigenetic Effectors.

Acute starvation can have long-term consequences that are mediated through epigenetic change. Some of these changes are affected by the activity of AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. In Caenorhabditis elegans, the absence of AMPK during a period of starvation in an early larval stage results in developmental defects following their recovery on food, while many of them become sterile. Moreover, the loss of AMPK during this quiescent period results in transgenerational phenotypes that can become progressively worse with each successive generation. Our recent data describe a chromatin-based mechanism of how AMPK mediates adjustment to acute starvation in the germ cells, however, the heritable aspect of this AMPK mutant phenotype remains unresolved. Here, we explore how AMPK might affect this process and speculate how the initial transcription that occurs in the germ cells may adversely affect subsequent germline gene expression and/or genomic integrity.

Demoinet E ，Roy R 《-》

Analysis of Transgenerational Phenotypes Following Acute Starvation in AMPK-Deficient C. elegans.

Demoinet E ，Roy R 《-》

AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans.

Demoinet E ，Li S ，Roy R 《-》

A global chromatin compaction pathway that represses germline gene expression during starvation.

While much is known about how transcription is controlled at individual genes, comparatively little is known about how cells regulate gene expression on a genome-wide level. Here, we identify a molecular pathway in the C. elegans germline that controls transcription globally in response to nutritional stress. We report that when embryos hatch into L1 larvae, they sense the nutritional status of their environment, and if food is unavailable, they repress gene expression via a global chromatin compaction (GCC) pathway. GCC is triggered by the energy-sensing kinase AMPK and is mediated by a novel mechanism that involves the topoisomerase II/condensin II axis acting upstream of heterochromatin assembly. When the GCC pathway is inactivated, then transcription persists during starvation. These results define a new mode of whole-genome control of transcription.

Belew MD ，Chien E ，Wong M ，Michael WM ... -  《-》

AMPK Regulates Developmental Plasticity through an Endogenous Small RNA Pathway in Caenorhabditis elegans.

Wong C ，Roy R 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》