Structures of three distinct activator–TFIID complexes

Liu, Wei Li; Coleman, Robert A.; Ma, Elizabeth; Grob, Patricia; Yang, Jason; Zhang, Yixi; Dailey, Gina M; Nogales, Eva; Tjian, Robert

doi:10.1101/gad.1790709

Cited by 59 publications

(102 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By contrast, removal of residues 253-344 (Fig. 1A, green-shaded domain) completely abolished Rap1 binding (lanes [11][12][13][14][15][16][17][18][19][20]. To test whether the Taf4 RBD is essential, we scored the ability of the TAF4 deletion family to support viability via a plasmid shuffle assay.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Direct Transactivator-Transcription Factor IID (TFIID) Contacts Drive Yeast Ribosomal Protein Gene Transcription

Layer

Miller

Weil

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Transcription factor IID (TFIID) plays a key role in regulating eukaryotic gene expression by directly binding promoters and enhancer-bound transactivator proteins. However, the precise mechanisms and outcomes of transactivator-TFIID interaction remain unclear. Transcription of yeast ribosomal protein genes requires TFIID and the DNA-binding transactivator Rap1. We have previously shown that Rap1 directly binds to the TFIID complex through interaction with its TATA-binding proteinassociated factor (Taf) subunits Taf4, -5, and -12. Here, we identify and characterize the Rap1 binding domains (RBDs) of Taf4 and Taf5. These RBDs are essential for viability but dispensable for Taf-Taf interactions and TFIID stability. Cells expressing altered Rap1 binding domains exhibit conditional growth, synthetic phenotypes when expressed in combination or with altered Rap1, and are selectively defective in ribosomal protein gene transcription. Taf4 and Taf5 proteins with altered RBDs bind Rap1 with reduced affinity. We propose that collectively the Taf4, Taf5, and Taf12 subunits of TFIID represent the physical and functional targets for Rap1 interaction and, furthermore, that these interactions drive ribosomal protein gene transcription. Activation of eukaryotic RNA polymerase II (pol II)2 -transcribed genes requires the action of an ensemble of proteins collectively referred to as coactivators (1, 2). These large multisubunit protein assemblies stimulate mRNA gene transcription at several distinct steps as follows: either by utilizing intrinsic enzymatic activities to alter the biochemical characteristics of transcription proteins and/or chromatin; facilitating accurate formation of preinitiation complexes (PICs) near the transcription start site; stimulating pol II activity; or by serving as scaffolds for the assembly of additional coactivators on target genes. Many variations of these mechanisms have been described, but it is generally accepted that coactivators are targeted by gene-specific enhancer-bound transactivator proteins. Transactivators are minimally composed of distinct DNA binding domains (DBDs) and activation domains (ADs). Classical studies have shown that ADs enhance transcription rates by directly stimulating the formation and/or function of the PIC, which is an assortment of over 40 distinct polypeptides often termed the general transcription factors

show abstract

Section: Resultsmentioning

confidence: 99%

“…For example, the transcription factors Sp1, c-Jun, CREB, TCF/Pan, HP1␣/␤, and Caenorhabditis elegans differentiation modulators OMA-1/2 all bind Taf4 (8,16,48). In addition, cell type-specific isoforms of Taf4 have been described in metazoans that contribute to the diversity of regulatory inputs impinging on TFIID (49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

Direct Transactivator-Transcription Factor IID (TFIID) Contacts Drive Yeast Ribosomal Protein Gene Transcription

Layer

Miller

Weil

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Coactivators represent an important and highly conserved class of factors that mediate and integrate signals to arrive at the appropriate level of gene expression for a particular condition. Coactivators, like the multiprotein complexes SAGA, Mediator, and TFIID, associate with the relevant promoter via protein-protein interactions with sequencespecific DNA-binding proteins (Brown et al 2001;Zhang et al 2004;Govind et al 2005;Thakur et al 2008;Liu et al 2009). Coactivators facilitate transcription by recruiting RNAPII and/or enhancing the formation of the preinitiation complex by a variety of mechanisms (Torchia et al 1998;Naar et al 2001;Kornberg 2005;Baker and Grant 2007).…”

Section: Discussionmentioning

confidence: 99%

Activation of a Poised RNAPII-Dependent Promoter Requires Both SAGA and Mediator

et al. 2010

View full text Add to dashboard Cite

A growing number of promoters have key components of the transcription machinery, such as TATAbinding protein (TBP) and RNA polymerase II (RNAPII), present at the promoter prior to activation of transcription. Thus, while transcriptional output undergoes a dramatic increase between uninduced and induced conditions, occupancy of a large portion of the transcription machinery does not. As such, activation of these poised promoters depends on rate-limiting steps after recruitment of TBP and RNAPII for regulated expression. Little is known about the transcription components required in these latter steps of transcription in vivo. To identify components with critical roles in transcription after recruitment of TBP in Saccharomyces cerevisiae, we screened for loss of gene expression activity from promoter-tethered TBP in .100 mutant strains deleted for a transcription-related gene. The assay revealed a dramatic enrichment for strains containing deletions in genes encoding subunits of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex and Mediator. Analysis of an authentic postrecruitment-regulated gene (CYC1) reveals that SAGA occupies the promoter under both uninduced and induced conditions. In contrast, Mediator is recruited only after transfer to inducing conditions and correlates with activation of the preloaded polymerase at CYC1. These studies indicate the critical functions of SAGA and Mediator in the mechanism of activation of genes with rate-limiting steps after recruitment of TBP.

show abstract

“…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.…”

mentioning

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.

173

View full text Add to dashboard Cite

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 ...

show abstract

Structures of three distinct activator–TFIID complexes

Cited by 59 publications

References 39 publications

Direct Transactivator-Transcription Factor IID (TFIID) Contacts Drive Yeast Ribosomal Protein Gene Transcription

Direct Transactivator-Transcription Factor IID (TFIID) Contacts Drive Yeast Ribosomal Protein Gene Transcription

Activation of a Poised RNAPII-Dependent Promoter Requires Both SAGA and Mediator

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

Contact Info

Product

Resources

About