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Transcriptional Regulation in Schizophrenia 105Figure 5-1 Schematic of a portion of chromatin illustrating that DNA (black strand) istightly wound around histones, which from nucleosomes (orange circles). In the cell,nucleosomes consist of eight histone proteins that form a core around which DNA is tightlywrapped and together form the fundamental structure of chromatin. In order to activatetranscription, the DNA must be exposed such that transcription factors (blue and yellowstars) and enzymes can initiate and continue transcription. This is accomplished by modifyinga portion of the histones, which in turn exposes regions of the DNA and also transcriptionfactors and other proteins to bind and transcription to proceed. As the black arrowin the figure indicates, chromatin can fluctuate between the open and closed state.cytosol) and the relevant introns must be removed. RNA editing and alternativesplicing are two additional mechanisms that increase genetic diversity withoutincreasing the overall number of genes. Once the mRNA is processed, it exits thenucleus and is translated into a protein (figure 5-2). Once outside the nucleus, themRNA is susceptible to degradation before translation such as destruction bymicroRNAs.Assuming the mRNA is not degraded or silenced and is available for translation,the process is initiated by ribosomal recognition of a methionine codon (figure5-2). The ability of the ribosome to recognize the correct codon can affect theexpression of the protein. Once the protein is synthesized, posttranslational modificationsincluding phosphorylation, glycosylation, acetylation, and disulfide bondformations alter the functionality of the protein in response to the cellular milieu.In the nervous system, the proteins must also be actively transported to the respectivesite of action.Regional Vulnerabilities and Gene ExpressionSchizophrenia is a complex psychiatric disorder involving an assortment of positive(hallucinations and delusions), negative (flattened affect and social withdrawal),and cognitive (deficits in working memory and executive function)symptoms. Multiple brain regions have been implicated in schizophrenic pathol-