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

Science, 3 September 2010
Vol. 329, Issue 5996, p. 1201-1205
DOI: 10.1126/science.1191241

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

  1. David Bungard1,
  2. Benjamin J. Fuerth2,3,
  3. Ping-Yao Zeng1,4,
  4. Brandon Faubert2,3,
  5. Nancy L. Maas1,
  6. Benoit Viollet5,6,
  7. David Carling7,
  8. Craig B. Thompson8,
  9. Russell G. Jones2,3,8,*,
  10. Shelley L. Berger1,9,10,*
  1. 1Department of Cellular and Developmental Biology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.
  2. 2Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada.
  3. 3Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada.
  4. 4Institutes of Biomedical Sciences Epigenetics Program, Mingdao Building, Room 511, Fudan University, Mail Box 281, 138 Yixue Yuan Road, Shanghai 200032, P.R. China.
  5. 5Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France.
  6. 6INSERM U1016, 75014 Paris, France.
  7. 7Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London W12 0NN, UK.
  8. 8Abramson Cancer Center and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
  9. 9Department of Genetics, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.
  10. 10Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
  1. *To whom correspondence should be addressed. E-mail: russell.jones{at} (R.G.J.); bergers{at} (S.L.B.)


The mammalian adenosine monophosphate–activated protein kinase (AMPK) is a serine-threonine kinase protein complex that is a central regulator of cellular energy homeostasis. However, the mechanisms by which AMPK mediates cellular responses to metabolic stress remain unclear. We found that AMPK activates transcription through direct association with chromatin and phosphorylation of histone H2B at serine 36. AMPK recruitment and H2B Ser36 phosphorylation colocalized within genes activated by AMPK-dependent pathways, both in promoters and in transcribed regions. Ectopic expression of H2B in which Ser36 was substituted by alanine reduced transcription and RNA polymerase II association to AMPK-dependent genes, and lowered cell survival in response to stress. Our results place AMPK-dependent H2B Ser36 phosphorylation in a direct transcriptional and chromatin regulatory pathway leading to cellular adaptation to stress.

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


D. Bungard, B. J. Fuerth, P.-Y. Zeng, B. Faubert, N. L. Maas, B. Viollet, D. Carling, C. B. Thompson, R. G. Jones, and S. L. Berger, Signaling Kinase AMPK Activates Stress-Promoted Transcription via Histone H2B Phosphorylation. Science 329, 1201-1205 (2010).

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