Adenovirus E1A products suppress myogenic differentiation and inhibit transcription from muscle-specific promoters

Keith A Webster, G. E O Muscat, L. Kedes

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Abstract

The primary function of the adenovirus E1A-region genes is to activate other adenoviral genes during a permissive viral infection by modifying the host cell transcriptional apparatus. Host cell immortalization, or transformation by the whole adenoviral early region, presumably results as a consequence of these modifications. Both transcriptional activation and transcriptional repression of non-adenoviral genes by the E1A proteins have been reported. It is currently not clear which, if either, of these activities contributes to host cell transformation and immortalization. Although there may be a physiological impact of some E1A-stimulated host cell genes, in many cases the functional significance is unclear. No common target sequences have been recognized in stimulated cellular genes and it has recently been proposed that in many cases, particularly involving newly transfected genes, available 'TATA-box' sequences may be the opportunistic beneficiaries of E1A assistance as a secondary consequence of E1A primary functions within the host cell nucleus. E1A-mediated transcriptional repression appears to be a more specific process insofar as common core elements are shared by the E1A-suppressed SV40, polyoma B, IgG heavy-chain and insulin enhancers. In the present communication we report that the complete myogenic programme of L8 and C2 myoblasts can be blocked by the introduction of constitutively expressing E1A genes, and show that the transcriptional induction of muscle-specific genes is inhibited. In particular, the promoter-inducing activities of well-defined elements that are required for the muscle-specific expression of the two sarcomeric α-actins, and which normally bind cellular trans-acting factors, become targets for E1A suppression. The results support the hypothesis that the suppression of differentiation by E1A products is effected by an E1A-mediated block in the transcriptional activation of cellular genes by specific developmentally regulated cis-acting promoter elements.

Original languageEnglish
Pages (from-to)553-557
Number of pages5
JournalNature
Volume332
Issue number6164
StatePublished - Jan 1 1988
Externally publishedYes

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