BACKGROUND: Silencing of normal gene expression occurs early in the apoptosis of 
neurons, well before the cell is committed to the death pathway, and has been 
extensively characterized in injured retinal ganglion cells. The causative 
mechanism of this widespread change in gene expression is unknown. We 
investigated whether an epigenetic change in active chromatin, specifically 
histone H4 deacetylation, was an underlying mechanism of gene silencing in 
apoptotic retinal ganglion cells (RGCs) following an acute injury to the optic 
nerve.
RESULTS: Histone deacetylase 3 (HDAC3) translocates to the nuclei of dying cells 
shortly after lesion of the optic nerve and is associated with an increase in 
nuclear HDAC activity and widespread histone deacetylation. H4 in promoters of 
representative genes was rapidly and indiscriminately deacetylated, regardless 
of the gene examined. As apoptosis progressed, H4 of silenced genes remained 
deacetylated, while H4 of newly activated genes regained, or even increased, its 
acetylated state. Inhibition of retinal HDAC activity with trichostatin A (TSA) 
was able to both preserve the expression of a representative RGC-specific gene 
and attenuate cell loss in response to optic nerve damage.
CONCLUSIONS: These data indicate that histone deacetylation plays a central role 
in transcriptional dysregulation in dying RGCs. The data also suggests that 
HDAC3, in particular, may feature heavily in apoptotic gene silencing.