Transcriptional Control Mechanisms in the Regulation of Cholesterol Balance

The mechanisms that govern regulation of cholesterol metabolism in higher eukaryotic cells provide an example of how metabolic regulation has evolved to establish growth and nutritional control in a multicellular environment. Two sources of cholesterol must be balanced to ensure optimum growth and viability. Much of the control is established by regulating the levels of key proteins involved in cholesterol uptake and biosynthesis and this occurs by alterations in promoter activity. The studies discussed here track the progression in understanding the mechanism for transcriptional regulation by cholesterol from the isolation of the key genes involved, to the careful dissection of the cis-acting sequences that control expression, and on to what is currently known about the trans-acting proteins that mediate the regulatory response.