This review examines the general hypothesis that cellular plasticity may be related to genomic plasticity. Using a novel approach to microarray analysis, recent studies from our laboratory showed that, in genetically identical mice, variability in the large-scale organization of gene expression was associated with individual differences in behavior. An association of the large-scale organization of gene expression in the hippocampus with behavioral variability suggests that an important aspect of gene expression regulation had gone unrecognized with traditional genomic approaches designed to look for specific differences in gene expression levels. Here we introduce the concept of a ‘genomic tone’ as a global genomic property related to the levels and balance between factors that generally promote and factors that generally inhibit gene expression. We suggest that genomic tone may be related to the plasticity of the gene expression system and may be an important target for developmental and therapeutic interventions.

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