Function of the c-Myc oncoprotein in chromatin remodeling and transcription

Deregulated expression of the c-inj,c proto-oncogene contributes to maligna nt progression of a variety of tumors. The c-Myc protein (or Myc) is a tran scription factor that positively or negatively regulates expression of dist inct sets of target genes. Transcriptional activation by Myc is mediated th rough dimerization with Max and binding to the DNA consensus sequence CA(C/ T)GTG (the E-box). Transcriptional inhibition is mediated through distinct DNA elements, and may be due to functional interference with factors that t ransactivate via these sequences. We review here our current knowledge on t hese transcriptional activities of Myc and their relationship to its biolog ical function. The findings that Myc interacts with subunits of histone ace tyl-transferase (HAT) complexes and of the ATP-dependent chromatin remodeli ng complex, SWI/SNF, suggest that localized changes in chromatin structure may mediate Myc function. We present a working hypothesis for the concerted action of HAT and SWI/SNF complexes in Myc-activated transcription and arg ue that this model should prompt re-thinking of the experimental strategies and criteria used to identify Myc target genes. (C) 2001 Elsevier Science B.V. All rights reserved.