A general mechanism for transcriptional synergy by eukaryotic activators

Abstract

One of the important regulatory concepts to emerge from studies of eukaryotic gene expression is that RNA polymerase II promoters and their upstream activators are composed of functional modules whose synergistic action regulates the transcriptional activity of a nearby gene. Biochemical analysis of synergy by ZEBRA, a non-acidic activator of the Epstein-Barr virus (EBV) lytic cycle, showed that the synergistic transcriptional effect of promoter sites and activation modules correlates with assembly of the TFIID:TFIIA (DA) complex in DNase I footprinting and gel shift assays. The activator-dependent DA complex differs from a basal DA complex by its ability to bind TFIIB stably in an interaction regulated by TATA-binding protein-associated factors (TAFs). TFIIB enhances the degree of synergism by increasing complex stability. Similar findings were made with the acidic activator GAL4-VP16. Our data suggest a unifying mechanism for gene activation and synergy by acidic and non-acidic activators, and indicate that synergy is manifested at the earliest stage of preinitiation complex assembly.

Transcriptional regulation of the hepatocyte growth factor (HGF) gene by the Sp family of transcription factors

“…In HGF expressing cells, other cis-acting elements both upstream/downstream of the Sp1 binding site in the HGF promoter may also cooperate with Sp1 to confer full promoter activity. This is consistent with the notion that synergy among multiple activators (such as Sp1) enhances preinitiation complex formation by promoting stabilized binding of TFIID to the promoter and subsequent recruitment of other basal transcription factors, whereas a single activator is unable to do so (Chi et al, 1995;Buratowski et al, 1995;Sauer et al, 1995).…”

Efficient Induction of Nuclear Aggresomes by Specific Single Missense Mutations in the DNA-binding Domain of a Viral AP-1 Homolog

“…The pathogenic domain of mutant Huntington disease protein (httex1p) containing expanded polyQ repeats has also been found to interact with CREB-binding protein (17). ZEBRA functionally interacts with TATA box-binding protein, another polyQ-containing protein implicated in spinocerebellar ataxia 17 (61)(62)(63). Aggresome formation by the ZEBRA mutants reported in this study may be mediated by interactions with the same polyQ proteins that interact with WT ZEBRA.…”

Positive and negative functions of the SAGA complex mediated through interaction of Spt8 with TBP and the N-terminal domain of TFIIA

“…The general factor TFIIA interacts directly with TBP and stabilizes TBP-DNA interactions (Weideman et al 1997;Hampsey 1998;Liu et al 1999). TFIIA also stimulates and stabilizes the binding of TFIID to DNA as part of an activator-TFIID-TFIIA-DNA complex, a rate-limiting intermediate in the transcription of certain promoters (Wang et al 1992;Lieberman and Berk 1994;Chi et al 1995). Finally, TFIIA can compete with negative factors such as NC2, Mot1, and the Taf1 TAND domain for binding to TBP (Hampsey 1998;Kokubo et al 1998;Ozer et al 1998b;Cang et al 1999).…”