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PMID:18754010

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Citation

Nott, A, Watson, PM, Robinson, JD, Crepaldi, L and Riccio, A (2008) S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons. Nature 455:411-5

Abstract

Brain-derived neurotrophic factor (BDNF) and other neurotrophins have a vital role in the development of the rat and mouse nervous system by influencing the expression of many specific genes that promote differentiation, cell survival, synapse formation and, later, synaptic plasticity. Although nitric oxide (NO) is known to be an important mediator of BDNF signalling in neurons, the mechanisms by which neurotrophins influence gene expression during development and plasticity remain largely unknown. Here we show that BDNF triggers NO synthesis and S-nitrosylation of histone deacetylase 2 (HDAC2) in neurons, resulting in changes to histone modifications and gene activation. S-nitrosylation of HDAC2 occurs at Cys 262 and Cys 274 and does not affect deacetylase activity. In contrast, nitrosylation of HDAC2 induces its release from chromatin, which increases acetylation of histones surrounding neurotrophin-dependent gene promoters and promotes transcription. Notably, nitrosylation of HDAC2 in embryonic cortical neurons regulates dendritic growth and branching, possibly by the activation of CREB (cyclic-AMP-responsive-element-binding protein)-dependent genes. Thus, by stimulating NO production and S-nitrosylation of HDAC2, neurotrophic factors promote chromatin remodelling and the activation of genes that are associated with neuronal development.

Links

PubMed Online version:10.1038/nature07238

Keywords

Animals; Brain-Derived Neurotrophic Factor/pharmacology; Chromatin/metabolism; Chromatin Assembly and Disassembly; Cysteine/metabolism; Cytoplasm/metabolism; Dendrites/metabolism; Female; Histone Deacetylase 2; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Male; Mice; Nerve Growth Factors/metabolism; Neurons/cytology; Neurons/enzymology; Neurons/metabolism; Nitric Oxide/biosynthesis; Nitric Oxide/metabolism; Nuclear Proteins/metabolism; Rats; Repressor Proteins/genetics; Repressor Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:B1WBY8

involved_in

GO:0010977: negative regulation of neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:F7ENH8

involved_in

GO:0010977: negative regulation of neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HDAC2

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HDAC2

involved_in

GO:0010977: negative regulation of neuron projection development

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P70288

P

Seeded From UniProt

complete

MOUSE:HDAC2

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HDAC2

enables

GO:0033558: protein deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:HDAC2

involved_in

GO:0010977: negative regulation of neuron projection development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HDAC2

involved_in

GO:0006476: protein deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HDAC2

part_of

GO:0000790: nuclear chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:HDAC2

involved_in

GO:0016358: dendrite development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HDAC2

enables

GO:0004407: histone deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:HDAC2

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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