Regulation of connexin expression.

Gap junctions contain cell-cell communicating channels that consist of multimeric proteins called connexins and mediate the exchange of low-molecular-weight metabolites and ions between contacting cells. Gap junctional communication has long been hypothesized to play a crucial role in the maintenance of homeostasis, morphogenesis, cell differentiation, and growth control in multicellular organisms. The recent discovery that human genetic disorders are associated with mutations in connexin genes and experimental data on connexin knockout mice have provided direct evidence that gap junctional communication is essential for tissue functions and organ development. Thus far, 21 human genes and 20 mouse genes for connexins have been identified. Each connexin shows tissue- or cell-type-specific expression, and most organs and many cell types express more than one connexin. Cell coupling via gap junctions is dependent on the specific pattern of connexin gene expression. This pattern of gene expression is altered during development and in several pathological conditions resulting in changes of cell coupling. Connexin expression can be regulated at many of the steps in the pathway from DNA to RNA to protein. However, transcriptional control is one of the most important points. In this review, we summarize recent knowledge on transcriptional regulation of connexin genes by describing the structure of connexin genes and transcriptional factors that regulate connexin expression.