histone deacetylase
S-nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons
28/08/2008
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 plasticity1. Although nitric
oxide (NO) is known to be an important mediator of
BDNF signalling in neurons2, 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.
Nature advance online publication 27 August 2008 | doi:10.1038/nature07238
Nature advance online publication 27 August 2008 | doi:10.1038/nature07238
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