Synergistic enhancement of both initiation and elongation by acidic transcription activation domains.

Abstract

The effects of activation domain synergy on transcription initiation and elongation have been examined utilizing a system that permits the targeting of a defined number of activation modules to promoter DNA. As predicted, incremental increases in targeted activation potential were found to result in corresponding increases in transcription initiation. Surprisingly, however, transcriptional processivity, and hence mRNA synthesis, required a threshold level of activation domain synergy that exceeded the level required for at least modest levels of transcription initiation. The degree to which transcriptional processivity was enhanced was shown to depend on the quantity of activation modules targeted to the promoter DNA, rather than the quality. While the RNA‐sequence specific HIV‐1 Tat trans‐activator was also shown to enhance processivity in this assay system, Tat differed from DNA‐sequence specific activation domains in exerting a more dramatic effect on the efficiency of transcript elongation.

Taking a new TAK on Tat transactivation

“…It is unlikely that Tat, TAR, or P-TEFb play any role in the maintenance of elongation at later stages in transcription, as this process is not sensitive to DRB, and because TAR need only be present transiently on the nascent transcript at early stages in transcription. It is interesting that Tat acts through RNA to regulate a step in elongation that apparently can otherwise be regulated by DNAbinding proteins (Blair et al 1996;Blau et al 1996). Two possible reasons for this are that regulation through RNA appears to be more effective (Blair et al 1996) and is required to prevent a concomitant increase in the levels of short transcripts that contain TAR and would otherwise sequester Tat and its coactivator complex away from the promoter .…”

“…A common rate-limiting step in the transcription of inducible eukaryotic genes is the release of RNA polymerase II (RNAPII) molecules from stalled elongation complexes that accumulate shortly after the initiation of RNA synthesis (Blair et al 1996;Blau et al 1996; for review, see Greenblatt et al 1993;Bentley 1995). In the absence of the inducer protein, transcription at these genes is usually initiated by RNAP complexes that pause at sites 20-60 nucleotides downstream of the promoter.…”

Modular organization of the E2F1 activation domain and its interaction with general transcription factors TBP and TFIIH

“…In certain of these cases, activation domains have been demonstrated to consist of minimal activation modules which, when reiterated, result in a synergistic activation of transcription (Tanaka and Herr, 1994;Blair et al, 1996), but the meaning of this observation has not been clear.…”

CA150, a Nuclear Protein Associated with the RNA Polymerase II Holoenzyme, Is Involved in Tat-Activated Human Immunodeficiency Virus Type 1 Transcription

“…At present, the mechanism by which Tat activates gene expression is unknown. In vitro and in vivo studies have not definitely distinguished between an effect of Tat on the initiation phase of transcription and an effect on the elongation phase of this process (4,5,13,18,26,35,42,43,49,50,63,67,76).…”