BACKGROUND: Histone acetylation of chromatin plays a key role in promoting the 
dynamic transcriptional responses in neurons that influence the neuroplasticity 
linked to cognitive ability, yet the specific histone acetyltransferases (HATs) 
that create such epigenetic marks remain to be elucidated.
METHODS AND FINDINGS: Here we use the Drosophila neuromuscular junction (NMJ) as 
a well-characterized synapse model to identify HATs that control synaptic 
remodeling and structure. We show that the HAT dTip60 is concentrated both pre 
and post-synaptically within the NMJ. Presynaptic targeted reduction of dTip60 
HAT activity causes a significant increase in synaptic bouton number that 
specifically affects type Is boutons. The excess boutons show a suppression of 
the active zone synaptic function marker bruchpilot, suggesting defects in 
neurotransmission function. Analysis of microtubule organization within these 
excess boutons using immunohistochemical staining to the microtubule associated 
protein futsch reveals a significant increase in the rearrangement of 
microtubule loop architecture that is required for bouton division. Moreover, 
α-tubulin acetylation levels of microtubules specifically extending into the 
terminal synaptic boutons are reduced in response to dTip60 HAT reduction.
CONCLUSIONS: Our results are the first to demonstrate a causative role for the 
HAT dTip60 in the control of synaptic plasticity that is achieved, at least in 
part, via regulation of the synaptic microtubule cytoskeleton. These findings 
have implications for dTip60 HAT dependant epigenetic mechanisms underlying 
cognitive function.