Transcriptional Regulation in<i>Saccharomyces cerevisiae</i>: Transcription Factor Regulation and Function, Mechanisms of Initiation, and Roles of Activators and Coactivators

Hahn, Steven; Young, Elton T.

doi:10.1534/genetics.111.127019

Cited by 308 publications

(332 citation statements)

References 443 publications

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“…These highly regulated factors contain one or more activation domains (ADs) that typically bind coactivators-the complexes that contact the transcription machinery and/or have chromatin modifying activity (1)(2)(3)(4)(5). AD-coactivator binding initiates a cascade of events leading to productive transcription including targeted chromatin remodeling and stimulation of both RNA polymerase II preinitiation complex formation and transcription elongation (6).…”

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confidence: 99%

A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface

Warfield

Tuttle

Pacheco

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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173

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Although many transcription activators contact the same set of coactivator complexes, the mechanism and specificity of these interactions have been unclear. For example, do intrinsically disordered transcription activation domains (ADs) use sequence-specific motifs, or do ADs of seemingly different sequence have common properties that encode activation function? We find that the central activation domain (cAD) of the yeast activator Gcn4 functions through a short, conserved sequence-specific motif. Optimizing the residues surrounding this short motif by inserting additional hydrophobic residues creates very powerful ADs that bind the Mediator subunit Gal11/Med15 with high affinity via a "fuzzy" protein interface. In contrast to Gcn4, the activity of these synthetic ADs is not strongly dependent on any one residue of the AD, and this redundancy is similar to that of some natural ADs in which few if any sequence-specific residues have been identified. The additional hydrophobic residues in the synthetic ADs likely allow multiple faces of the AD helix to interact with the Gal11 activator-binding domain, effectively forming a fuzzier interface than that of the wild-type cAD.Mediator complex | protein NMR T ranscription activators are regulators of cell identity, cell growth, and the response to environmental conditions. These highly regulated factors contain one or more activation domains (ADs) that typically bind coactivators-the complexes that contact the transcription machinery and/or have chromatin modifying activity (1-5). AD-coactivator binding initiates a cascade of events leading to productive transcription including targeted chromatin remodeling and stimulation of both RNA polymerase II preinitiation complex formation and transcription elongation (6). Many broadly acting ADs bind several coactivators, allowing them to function at a wide range of promoters with different coactivator requirements (7)(8)(9)(10)(11)(12)(13)(14). The function of most tested ADs is conserved among eukaryotes (15, 16), even though some key activator targets are not conserved. For example, the herpes virus protein VP16 strongly activates transcription in both yeast and mammalian cells, although human Med25, a critical target of VP16 in humans, is not found in yeast (17,18). Thus, the ability to adapt to different coactivator targets is seemingly a key property of ADs.Defining what constitutes a functional AD has been difficult, because there is little apparent sequence similarity among different ADs. All structurally characterized eukaryotic ADs lack a stable 3D structure and are disordered in the absence of a coactivator target (19)(20)(21)(22)(23)(24)(25). Initial studies classified ADs based on enriched residues: acidic proline-, glutamine-, or serine-rich activators (26). However, these residue types later were found to be generally enriched in intrinsically disordered proteins and were termed "disorder-promoting residues" (27, 28).Attempts to define functional sequence motifs within ADs have led to ambiguous results. For many ...

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confidence: 99%

A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface

Warfield

Tuttle

Pacheco

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

173

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“…RNA polymerase II and the general RNA polymerase II transcription factors (TFIIA, 3 -B, -D, -E, -F, and -H) are required for mRNA gene transcription in all eukaryotes (1,2). These factors assemble at gene promoters to form the preinitiation complex (PIC), a macromolecular assembly required for accurate initiation of transcription.…”

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confidence: 99%

“…Third, in metazoan TFIID, Tafs 1 and 2 bind to the initiator (INR) core promoter element (10,12), and Tafs 6 and 9 bind to the downstream promoter element (11). Neither the INR nor the downstream promoter element has been unambiguously identified in the yeast system (1).…”

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confidence: 99%

The C Terminus of the RNA Polymerase II Transcription Factor IID (TFIID) Subunit Taf2 Mediates Stable Association of Subunit Taf14 into the Yeast TFIID Complex

Feigerle

Weil

2016

Journal of Biological Chemistry

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The evolutionarily conserved RNA polymerase II transcription factor D (TFIID) complex is composed of TATA box-binding protein (TBP) and 13 TBP-associated factors (Tafs). The mechanisms by which many Taf subunits contribute to the essential function of TFIID are only poorly understood. To address this gap in knowledge, we present the results of a molecular genetic dissection of the TFIID subunit Taf2. Through systematic site-directed mutagenesis, we have discovered 12 taf2 temperature-sensitive (ts) alleles. Two of these alleles display growth defects that can be strongly suppressed by overexpression of the yeast-specific TFIID subunit TAF14 but not by overexpression of any other TFIID subunit. In Saccharomyces cerevisiae, Taf14 is also a constituent of six other transcription-related complexes, making interpretation of its role in each of these complexes difficult. Although Taf14 is not conserved as a TFIID subunit in metazoans, it is conserved through its chromatinbinding YEATS domain. Based on the Taf2-Taf14 genetic interaction, we demonstrate that Taf2 and Taf14 directly interact and mapped the Taf2-Taf14 interaction domains. We used this information to identify a Taf2 separation-of-function variant (Taf2-⌬C). Although Taf2-⌬C no longer interacts with Taf14 in vivo or in vitro, it stably incorporates into the TFIID complex. In addition, purified Taf2-⌬C mutant TFIID is devoid of Taf14, making this variant a powerful reagent for determining the role of Taf14 in TFIID function. Furthermore, we characterized the mechanism through which Taf14 suppresses taf2 ts alleles, shedding light on how Taf2-Taf14 interaction contributes to TFIID complex organization and identifying a potential role for Taf14 in mediating TFIID-chromatin interactions.RNA polymerase II and the general RNA polymerase II transcription factors (TFIIA,

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“…Different Pol II-associated factors are required for transcription initiation, RNA chain elongation through chromatin, pre-mRNA 5′-capping, splicing, 3′-RNA processing of the nascent transcript, and transcription termination (1)(2)(3). To understand how these factors cooperate with Pol II and achieve their functions, structural information on Pol II in complex with transcription factors is required.…”

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confidence: 99%

Structures of RNA polymerase II complexes with Bye1, a chromatin-binding PHF3/DIDO homologue

Kinkelin

Wozniak

Rothbart

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Bypass of Ess1 (Bye1) is a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. Here we show that Bye1 binds with its TFIIS-like domain (TLD) to RNA polymerase (Pol) II, and report crystal structures of the Bye1 TLD bound to Pol II and three different Pol II-nucleic acid complexes. Like TFIIS, Bye1 binds with its TLD to the Pol II jaw and funnel. In contrast to TFIIS, however, it neither alters the conformation nor the in vitro functions of Pol II. In vivo, Bye1 is recruited to chromatin via its TLD and occupies the 5′-region of active genes. A plant homeo domain (PHD) in Bye1 binds histone H3 tails with trimethylated lysine 4, and this interaction is enhanced by the presence of neighboring posttranslational modifications (PTMs) that mark active transcription and conversely is impaired by repressive PTMs. We identify putative human homologs of Bye1, the proteins PHD finger protein 3 and death-inducer obliterator, which are both implicated in cancer. These results establish Bye1 as the founding member of a unique family of chromatin transcription factors that link histones with active PTMs to transcribing Pol II.gene transcription | chromatin modification F or transcription of eukaryotic protein-coding genes, RNA polymerase (Pol) II associates transiently with dozens of transcription factors. Different Pol II-associated factors are required for transcription initiation, RNA chain elongation through chromatin, pre-mRNA 5′-capping, splicing, 3′-RNA processing of the nascent transcript, and transcription termination (1-3). To understand how these factors cooperate with Pol II and achieve their functions, structural information on Pol II in complex with transcription factors is required. Thus far, X-ray crystallographic structural information on such complexes is limited to two transcription factors: the initiation factor TFIIB (4-7), and the elongation factor TFIIS (8-11). TFIIS contains three domains, a mobile N-terminal domain, a central domain that binds directly to the Pol II jaw and funnel domains, and a C-terminal zinc ribbon domain that inserts into the polymerase pore (also called the secondary channel) and reaches the Pol II active site (9), to stimulate cleavage of backtracked RNA during transcriptional proofreading and escape from arrest (12).In the yeast Saccharomyces cerevisiae, there is only a single protein that contains a domain that is distantly homologous to the central, Pol II-associated domain of TFIIS. This protein, bypass of Ess1 (Bye1), has been identified as a multicopy suppressor of Ess1 (13), a peptidyl-prolyl cis-trans isomerase involved in proline isomerization of the C-terminal domain (CTD) of Pol II (14, 15). In Bye1, the central TFIIS-like domain (TLD, residues 232-365) is flanked by an N-terminal plant homeo domain (PHD) (residues 74-134) and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain (residues 447-547; Fig. 1A). PHD domains are mostly found in proteins involved in chromatinmediated gene regulation (16). Con...

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Transcriptional Regulation inSaccharomyces cerevisiae: Transcription Factor Regulation and Function, Mechanisms of Initiation, and Roles of Activators and Coactivators

Cited by 308 publications

References 443 publications

A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface

A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface

The C Terminus of the RNA Polymerase II Transcription Factor IID (TFIID) Subunit Taf2 Mediates Stable Association of Subunit Taf14 into the Yeast TFIID Complex

Structures of RNA polymerase II complexes with Bye1, a chromatin-binding PHF3/DIDO homologue

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