Helix-loop-helix proteins as regulators of muscle-specific transcription.

Abstract

Unraveling the mechanisms that control cell type-specific tran- scription represents a major challenge for molecular biologists. The genes expressed by a differentiated cell depend on the cell’s unique developmental history and the integration of diverse extracellular signals that regulate intracellular pathways of signal transduction. Skeletal muscle provides an attractive system for analyzing the roles of cell identity and extracellular signals in the control of cell type-specific transcription. Myoblast differentiation is accompanied by the transcriptional activation of a large set of muscle-specific genes, many of which have been cloned and characterized. In addition, skeletal muscle cells can be maintained in tissue culture as established cell lines that recapitulate the events associated with myoblast differentiation in vivo. The pro- gram for muscle-specific transcription is also regulated by numerous growth factor and oncogenic signaling pathways, making this system amenable to investigations of the regulatory interactions between the cellular circuits that control cell proliferation and differentiation. The recent cloning of the MyoD family of myogenic regulators, which can directly activate skeletal muscle-specific genes and convert a wide range of cell types into skeletal muscle, has provided insight into the mechanisms that regulate muscle-spe-cific transcription and has revealed basic regulatory strategies that may control cell type-specific transcription in other special-ized cell types (for reviews, see Refs. 1-3). While other cell type- specific transcription factors have been identified, members of the MyoD family are unique thus far in their abilities to orches- trate an entire program of cell differentiation and to activate and maintain their own transcription. This review will focus on the role of the MyoD family in the control of muscle-specific transcription, on the influence of extracellular signals