The ZEBRA activation domain: modular organization and mechanism of action.

Abstract

An RNA polymerase II activator often contains several regions that contribute to its potency, an organization ostensibly analogous to the modular architecture of promoters and enhancers. The regulatory significance of this parallel organization has not been systematically explored. We considered this problem by examining the activation domain of the Epstein-Barr virus transactivator ZEBRA. We The ATP requirement may be for TFIIH, which acts as both a kinase and an ATP-dependent helicase (31).Activators are often classified according to the amino acid composition of their activation domains or regions. It has been proposed that different classes of activation domains may function by different mechanisms (37). Acidic activation regions are rich in acidic amino acids and have a net negative charge. Recent mechanistic studies have shown that GAL4-derived acidic activators (5, 28), containing the GAL4 DNA binding domain fused to various acidic activation regions (41), act by promoting transcription complex assembly (29,54). Furthermore, the synergistic effect of the GAL4 derivatives on transcription (a single activator is either impotent or marginally active, whereas two or more activators elicit a greater than additive response [5]) correlates with a synergistic increase in the number of open complexes (55). Recruitment and kinetic experiments suggest that acidic activators target early steps in preinitiation complex formation (8,18,29,47,53,55,56), including assembly of subcomplexes requiring TFIIA and TFIID (55) or TFIIB and TFIID (29,47). Although a mechanism for how acidic activators function is emerging, little is known about how other classes of activation domains work. It is noteworthy, however, that affinity chromatography and far-Western blotting experiments have implicated factors involved in early steps in complex assembly as potential targets of both acidic and nonacidic activators (23,25,27,30,46).An activator often contains two or more activation regions, or subdomains, distinguished by their locations within the activator and by their chemical compositions (37). Depending upon the particular study, these activation regions act either synergistically, additively, or redundantly to influence the activator's potency (13,17,21,32,38,48,49,52). It has been noted (13) that the organization and function of the multiple activation regions are superficially analogous to the modular structure of promoters and enhancers (7,39, 7045 on May 9, 2018 by guest

Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs

“…It is also reported that the isomerized D-A complex is sufficient for gene activation (Chi and Carey 1996). Certain gene activators and coactivators could facilitate the formation of D-A complex, but the mechanism has not been fully clarified (White et al 1992;Chi and Carey 1993;Ge and Roeder 1994;Shykind et al 1995). In this study, we indicate that miRNAs enhance the binding of TBP and TFIIA to gene core promoter, and facilitate the assembly of the PICs containing these general transcription factors (Fig.…”

A mechanism for TAFs in transcriptional activation: activation domain enhancement of TFIID-TFIIA--promoter DNA complex formation.

“…The functional significance of this interaction was demonstrated in studies with a TFIIB deletion mutant that fails to bind the VP16 activation domain and has lost the ability to support activated, but not basal, transcription (Roberts et al 1993). Finally, TFIIA has been implicated as a functional target of GAL4-AH and Zta, which appear to overcome the slow assembly of a TFIIA-TFIID--promoter complex (Wang et al 1992;Chi and Carey 1993).…”

bZIP proteins of human gammaherpesviruses

“…The first indication for this came from the work of Lieberman and Berk who demonstrated that not only do Zta and TBP interact directly, but the interaction stabilizes the association of TFIID with the TATA element (Lieberman & Berk, 1991). This was followed by studies describing the formation of stable initiation complexes containing Zta (Lieberman & Berk, 1991, 1994Chi & Carey, 1993Lieberman, 1994;Chi et al, 1995a, b;Ozer et al, 1996;Lieberman et al, 1997;Berk et al, 1998;Ellwood et al, 1999;Deng et al, 2001). Although it is inferred that the interaction between Zta and the general transcriptional machinery promotes transcription of ZRE-containing promoters, it remains an open question whether the interaction of Zta with the basic transcriptional machinery affects the expression of genes that do not contain a ZRE.…”