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S-nitrosylation of HDAC2 regulates the expression of the chromatin-remodeling factor Brm during radial neuron migration

  1. Antonella Riccioa,d,2
  1. aMedical Research Council Laboratory for Molecular Cell Biology, and
  2. dDepartment of Neuroscience, Physiology, and Pharmacology, University College London, London, WC1E 6BT, United Kingdom;
  3. bDepartment of Neuroscience and Pharmacology, University Medical Center, Utrecht 3584 CG, The Netherlands;
  4. cCenter for Neuroscience, Swammerdam Institute for Life Sciences, Science Park University of Amsterdam, Amsterdam 1098 XH, The Netherlands; and
  5. eInstitute Pasteur Unit of Epigenetic Regulation, 75724 Paris, France

  1. Edited* by Solomon H. Snyder, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved December 26, 2012 (received for review October 18, 2012)

Abstract

Dynamic epigenetic modifications play a key role in mediating the expression of genes required for neuronal development. We previously identified nitric oxide (NO) as a signaling molecule that mediates S-nitrosylation of histone deacetylase 2 (HDAC2) and epigenetic changes in neurons. Here, we show that HDAC2 nitrosylation regulates neuronal radial migration during cortical development. Bead-array analysis performed in the developing cortex revealed that brahma (Brm), a subunit of the ATP-dependent chromatin-remodeling complex BRG/brahma-associated factor, is one of the genes regulated by S-nitrosylation of HDAC2. In the cortex, expression of a mutant form of HDAC2 that cannot be nitrosylated dramatically inhibits Brm expression. Our study identifies NO and HDAC2 nitrosylation as part of a signaling pathway that regulates cortical development and the expression of Brm in neurons.

Footnotes

  • ↵1J.N. and J.V.V. contributed equally to this study.

  • ↵2To whom correspondence should be addressed. E-mail: a.riccio{at}ucl.ac.uk.

  • Author contributions: A.N., J.V.V., M.P.S., and A.R. designed research; A.N., J.N., J.V.V., S.S., A.A.H.A.D., P.S., C.M., and A.R. performed research; C.M. and R.J.P. contributed new reagents/analytic tools; A.N., J.N., J.V.V., S.S., A.A.H.A.D., P.S., M.P.S., and A.R. analyzed data; and A.N., J.V.V., and A.R. wrote the paper.

  • The authors declare no conflict of interest.

  • ↵*This Direct Submission article had a prearranged editor.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1218126110/-/DCSupplemental.

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