A hypothetical model for the role of HDAC2 in transcriptional repression of synaptic plasticity genes in neuronal cells infected with HIV and/or in the presence of nicotine. During the gene transcription, the DNA to be transcribed is associated with histone proteins (blue) that are modified by the addition of acetyl groups (green). This modification results in a relaxed chromatin configuration that allows the transcriptional machinery access to the DNA. Up-regulation of HDAC2 during HIV infection and/or nicotine treatment leads to deletion of acetyl groups from histone proteins, resulting in a condensed chromatin that limits the binding of the transcriptional machinery, thereby decreasing gene transcription. Thus, inhibition of HDAC2 by using vorinostat may block these enzymatic processes and return the chromatin to a relaxed state, allowing gene transcription.