Eukaryotic Transcription Activation: Right on Target

Howard Hughes Medical Institute, Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Molecular Cell (Impact Factor: 14.02). 06/2005; 18(4):399-402. DOI: 10.1016/j.molcel.2005.04.017
Source: PubMed


The unambiguous identification of the direct targets of eukaryotic transcriptional activators has been a major challenge in the field. Recently, the authentic targets of several yeast and mammalian activators have been determined, and the results of these studies have important implications for our understanding of transcriptional activation mechanisms.

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    • "Generally, transcriptional activation begins with the binding of transcription factors to distal enhancer and promoter elements, which initiates the recruitment of coactivators and facilitates the binding of the general transcription machinery and the assembly of the RNA polymerase-II-containing preinitiation complex (PIC) at the core promoter (Green, 2005). Transcription factors can also promote steps in the transcription process subsequent to PIC assembly (which is of interest for the reprogramming factor cMyc) (Green, 2005). Importantly, the packaging of DNA into nucleosomes affects all aspects of transcription, from transcription factor binding to PIC formation and transcriptional elongation (Beato and Eisfeld, 1997; Li et al., 2007). "
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    • "The other nonessential components play important roles in SAGA function and gene expression [47] [48]. The essential component, Tra1, has been implicated as the target of several activators [17] [24] [27]. TAFs have been shown to play important roles for SAGA function and hence transcription activation [16] [52]. "
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    ABSTRACT: A growing number of human diseases are linked to abnormal gene expression which is largely controlled at the level of transcriptional initiation. The gene-specific activator promotes the initiation of transcription through its interaction with one or more components of the transcriptional initiation machinery, hence leading to stimulated transcriptional initiation or activation. However, all activator proteins do not target the same component(s) of the transcriptional initiation machinery. Rather, they can have different target specificities, and thus, can lead to distinct mechanisms of transcriptional activation. Two such distinct mechanisms of transcriptional activation in yeast are mediated by the SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID (Transcription factor IID) complexes, and are termed as "SAGA-dependent" and "TFIID-dependent" transcriptional activation, respectively. SAGA is the target of the activator in case of SAGA-dependent transcriptional activation, while the targeting of TFIID by the activator leads to TFIID-dependent transcriptional activation. Both the SAGA and TFIID complexes are highly conserved from yeast to human, and play crucial roles in gene activation among eukaryotes. The regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID are discussed here. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough!
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    • "While an increasing number of transcriptional activators have been identified, the direct targets or interacting partners of most transcriptional activators and the detailed mechanisms through which these interacting partners induce transcription initiation remain largely unknown. To date, only a few protein factors have been explicitly identified as direct targets of transcriptional activators, including the TATA box-binding protein (TBP), TFIIB, TFIIH, and a few others [6]. "
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    ABSTRACT: Eukaryotic transcription activators normally consist of a sequence-specific DNA-binding domain (DBD) and a transcription activation domain (AD). While many sequence patterns and motifs have been defined for DBDs, ADs do not share easily recognizable motifs or structures. We report herein that the N-terminal domain of yeast valyl-tRNA synthetase can function as an AD when fused to a DNA-binding protein, LexA, and turn on reporter genes with distinct LexA-responsive promoters. The transcriptional activity was mainly attributed to a five-residue peptide, WYDWW, near the C-terminus of the N domain. Remarkably, the pentapeptide per se retained much of the transcriptional activity. Mutations which substituted tryptophan residues for both of the non-tryptophan residues in the pentapeptide (resulting in W5) significantly enhanced its activity (~1.8-fold), while mutations which substituted aromatic residues with alanine residues severely impaired its activity. Accordingly, a much more active peptide, pentatryptophan (W7), was produced, which elicited ~3-fold higher activity than that of the native pentapeptide and the N domain. Further study indicated that W7 mediates transcription activation through interacting with the general transcription factor, TFIIB. Since W7 shares no sequence homology or features with any known transcription activators, it may represent a novel class of AD.
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