Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 8, Pages 3113-3118Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1218126110
Keywords
neural development; transcription; nitric oxide synthase; polar morphology; schizophrenia
Categories
Funding
- Medical Research Council [G0500/792, G0802010]
- Netherlands Organization for Health Research and Development Grant ZonMW-VIDI
- Netherlands Organization for Health Research and Development Grant ZonMW-TOP
- Netherlands Organization for Scientific Research VICI Grant [865.09.002]
- MRC [G0802010] Funding Source: UKRI
- Medical Research Council [G0802010, 973098] Funding Source: researchfish
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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.
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