Report

Signaling Kinase AMPK Activates Stress-Promoted Transcription via Histone H2B Phosphorylation

See allHide authors and affiliations

Science  15 Jul 2010:
1191241
DOI: 10.1126/science.1191241

Abstract

The mammalian AMP-activated protein kinase (AMPK) is a serine/threonine kinase protein complex that is a central regulator of cellular energy homeostasis (1, 2). However, the mechanisms by which AMPK mediates cellular responses to metabolic stress remain unclear. Here, we demonstrate that AMPK activates transcription through direct association with chromatin and phosphorylation of histone H2B at Serine-36. AMPK recruitment and H2B S36 phosphorylation colocalize within genes activated by AMPK-dependent pathways, and occur both in promoters and transcribed regions. Ectopic expression of S36A-substituted H2B reduces transcription and RNA polymerase II association to AMPK-dependent genes, and lowers cell survival in response to stress. Our results place AMPK-dependent H2B S36 phosphorylation in a direct transcriptional and chromatin regulatory pathway leading to cellular adaptation to stress.