Calcium fluxes and gene expression

Calcium fluxes modulate many biological processes including gene expression , and especially transcription. In this review, we describe the main possib le sources of calcium, namely the internal stores and extracellular milieu, as well as the channels that connect them to the cytosol. Calcium influxes activate calmodulin (CaM), a calcium-binding protein, which in turn switch es on several kinases (CaM-kinases, CaMK) and a phosphatase (calcineurin). The signalling pathway downstream the Ca2+-CaM complex also includes the Ca M-kinases kinases (CaMKK), thus elaborating a CaMK cascade that can cross-t alk with other pathways such as the MAP-kinase cascade. The calcium message is discussed in terms of time and space: the transcriptional response depe nds on the subcellular compartment and on the frequency/duration of the sti muli. Calcium can mo ulate transcription by modifying not only the localisa tion and activity of transcription factors, but also RNA polymerases proces sivity and chromatin structure. All these processes act in concert to regul ate calcium-dependent transcription. While most of these transactions are m ediated by Ca2+-CaM, a recently discovered calcium-sensitive transcriptiona l repressor, DREAM, directly binds calcium ions. This binding dramatically changes its DNA binding properties.