S-nitrosylation of HDAC2 regulates the expression of the chromatin-remodeling factor Brm during radial neuron migration.
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.
Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, United Kingdom.
Alexi
A
Nott
Justyna
J
Nitarska
Jesse V
JV
Veenvliet
Stephan
S
Schacke
Alwin A H A
AA
Derijck
Piotr
P
Sirko
Christian
C
Muchardt
R Jeroen
RJ
Pasterkamp
Marten P
MP
Smidt
Antonella
A
Riccio
D000818:Animals; D002465:Cell Movement; D002469:Cell Separation; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D018274:Electroporation; D005260:Female; D005434:Flow Cytometry; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology*; D009569:Nitric Oxide / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
C499503:Smarca2 protein, mouse; D014157:Transcription Factors; D009569:Nitric Oxide; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2