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Published Online July 15, 2010
Science DOI: 10.1126/science.1191241

Reports

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

David Bungard,1 Benjamin J. Fuerth,2,3 Ping Y. Zeng,1,4 Brandon Faubert,2,3 Nancy L. Mass,1 Benoit Viollet,5,6 David Carling,7 Craig B. Thompson,8 Russell G. Jones,2,3,8,* Shelley L. Berger1,*

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.

1 Department of Cellular and Developmental Biology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.
2 Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada.
3 Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada.
4 Institutes of Biomedical Sciences Epigenetics Program, Mingdao Building, Room 511, Fudan University, Mail Box 281, 138 Yixue Yuan Road, Shanghai 200032, P.R. China.
5 Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR 8104) INSERM U567, 75014 Paris, France.
6 INSERM U567, 75014 Paris, France.
7 Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London W12 0NN, UK.
8 Abramson Cancer Center and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.

* To whom correspondence should be addressed. E-mail: russell.jones{at}mcgill.ca (R.G.J.); bergers{at}mail.med.upenn.edu (S.L.B.)

Received for publication 21 April 2010. Accepted for publication 23 June 2010.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Targeting the Core of Transcription.
D. G. Hardie (2010)
Science 329, 1158-1159
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Science. ISSN 0036-8075 (print), 1095-9203 (online)