Regulation of tissue-specific glycolytic isozyme genes: coordinate response to oxygen availability in myogenic cells

Abstract

The steady-state levels of glycolytic isozymes in higher eucaryotic cells result from the coordinated expression of multiple unlinked genes. The tissue-specific isozyme profiles that characterize the expression of these genes are the result of adaptive evolutionary selection and form the primary basis for physiological regulation of the pathway. This review addresses some of the molecular mechanisms that may contribute to the regulation of these genes, both during development and in response to physiological perturbations in mature tissues. The evidence favors mechanisms of programmed "gene activation" accompanied by the concurrent activation of tissue-specific coordinating trans-acting cellular factors that determine transcriptional efficiencies of both regulatory and nonregulatory glycolytic isozymes. Based upon data from higher and lower eucaryotes, it is predicted that tissue-specific glycolytic isozyme genes have common cis-acting regions in their promoters to bind the cellular transcription factors. These regulatory sequences allow the unlinked genes to respond coordinately to physiological and developmental signals.