Regulation of Gene Expression

For all living cells, regulation of gene expression by extracellular signals is a fundamental mechanism of development, homeostasis, and adaptation to the environment. Indeed, the ultimate step in many signal transduction pathways is the modification of transcription factors that can alter the expression of specific genes. Thus, neurotransmitters, growth factors, and drugs are all capable of altering the patterns of gene expression in a cell. Such transcriptional regulation plays many important roles in nervous system functioning, including the formation of long-term memories. For many drugs, which require prolonged administration for their clinical effects (e.g., antidepressants, antipsychotics), the altered pattern of gene expression represents therapeutic adaptations to the initial acute action of the drug. Mechanisms that underlie the control of gene expression are becoming increasingly well understood. Every conceivable step in the process is subject to dynamic regulation in the cell. This includes structural changes in the chromatin to make a particular gene accessible for transcription, transcription of DNA into RNA, splicing of RNA into mRNA, editing and other covalent modifications of the mRNA, translation of mRNA into protein, and, finally, post-translational modification of the protein into its mature, functional form. Molecular details of each of these regulatory steps are becoming increasingly available. In this chapter, we focus on the regulation of gene expression by transcription factors because their role in mediating the ability of extracellular signals to alter gene expression remains the best characterized.