Coordinated gene transcription within mammalian nuclei in response to external stimuli is a highly orchestrated process involving the interplay between epigenetics-mediated chromatin remodeling and RNA polymerase-mediated transcription. The emergence of the concept of transcription factories (TFs), characterized as specialized nuclear subcompartments enriched in hyperphosphorylated RNAPII, suggests the potential for an additional mechanism directing coordinated and efficient gene transcription. While these transcriptional ‘hot spots’ have been implicated in the co-regulation of partner genes in other cell types, its presence in hippocampal neurons and its role in activity-dependent transcriptional control within the brain remains relatively unexplored. Furthermore, while previous findings indicate a functional relevance of histone acetylation in activity-dependent gene expression, the full array of histone acetyltransferases (HATs) involved in this process remain to be determined. Our findings reveal altered HAT Tip60 intranuclear dynamics and binding patterns on activity-dependent synaptic plasticity genes following rat hippocampal neuron stimulation. Utilizing immuno-DNA FISH, we show that neuronal stimulation alters the localization of these genes within the nucleus, corresponding to the mobilization of these co-regulated genes to RNAPII-rich TFs. Lastly, we show that Tip60 is found within the same TFs as the co-regulated synaptic plasticity genes following neuronal stimulation. Taken together, these data suggest that specific, directed compartmentalization of target genes, HATs and transcription machinery within hippocampal nuclei occurs following the introduction of external stimuli thereby enabling efficient, coordinated gene transcription. Our findings provide insights into a fundamental physiological gene expression paradigm governing transcriptional activation of co-regulated genes in response to external stimuli in hippocampal neurons.M.S., Neuroscience -- Drexel University, 201
