CRACKing the histone code: Cocaine's effects on chromatin structure and function

Epigenetics, the nongenetic component of how chromatin structure influences gene expression, is amazingly complex, and linking how environmental stimuli can influence epigenetic ‘gene programs’ in specific nerve cells to ultimately control behavior is a seemingly insurmountable puzzle. Cocaine is a highly potent stimulus capable of influencing behavior for the lifetime of an organism. Not surprisingly, psychostimulant-induced epigenetic regulation of gene expression has thus been identified as key to understanding the pathology of addiction. In addition to identifying this essential role of epigenetics in addiction, several important concepts have emerged such as the importance of global, temporal, and spatial control of mRNA expression in considering any given histone modification's influence on a given gene. Adding to this complexity, one has to account for the cumulative influence of other epigenetic modifications on a gene's transcription in addition to the interplay between transcription factors and chromatin structure. This review highlights how bioinformatic, molecular, and behavioral studies on addiction provide new insight into these concepts and outlines two distinct psychostimulant-induced patterns of chromatin regulation which are thought to underlie unique programs of gene expression that contribute importantly to the addicted state.