Novel isoforms of the TFIID subunit TAF4 modulate nuclear receptor-mediated transcriptional activity

Brunkhorst, Adrian; Neuman, Toomas; Hall, Anita; Arenas, Ernest; Bartfai, Tamás; Hermanson, Ola; Metsis, Madis

doi:10.1016/j.bbrc.2004.10.078

Cited by 9 publications

(9 citation statements)

References 134 publications

(193 reference statements)

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“…Our data, along with published findings [30], shows a broad distribution of alternative splice variants across cells and tissues of TAF4 alternative mRNAs. Here, we show that across the TAF4 gene, alternative splicing predominantly targets exons VI and VII.…”

Section: Discussionsupporting

confidence: 87%

“…In Drosophila , two isoforms, TAF1-1 and TAF1-2, differ in their DNA binding activities and contribution to gene-specific transcription [29]. Currently, five alternatively spliced murine Taf4 mRNAs have been described [30]. These splice variants encode protein isoforms that differ in the structure of their TAFH and CRII domains and affinity for different nuclear receptors.…”

Section: Introductionmentioning

confidence: 99%

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Alternative Splicing Targeting the hTAF4-TAFH Domain of TAF4 Represses Proliferation and Accelerates Chondrogenic Differentiation of Human Mesenchymal Stem Cells

et al. 2013

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Transcription factor IID (TFIID) activity can be regulated by cellular signals to specifically alter transcription of particular subsets of genes. Alternative splicing of TFIID subunits is often the result of external stimulation of upstream signaling pathways. We studied tissue distribution and cellular expression of different splice variants of TFIID subunit TAF4 mRNA and biochemical properties of its isoforms in human mesenchymal stem cells (hMSCs) to reveal the role of different isoforms of TAF4 in the regulation of proliferation and differentiation. Expression of TAF4 transcripts with exons VI or VII deleted, which results in a structurally modified hTAF4-TAFH domain, increases during early differentiation of hMSCs into osteoblasts, adipocytes and chondrocytes. Functional analysis data reveals that TAF4 isoforms with the deleted hTAF4-TAFH domain repress proliferation of hMSCs and preferentially promote chondrogenic differentiation at the expense of other developmental pathways. This study also provides initial data showing possible cross-talks between TAF4 and TP53 activity and switching between canonical and non-canonical WNT signaling in the processes of proliferation and differentiation of hMSCs. We propose that TAF4 isoforms generated by the alternative splicing participate in the conversion of the cellular transcriptional programs from the maintenance of stem cell state to differentiation, particularly differentiation along the chondrogenic pathway.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Alternative Splicing Targeting the hTAF4-TAFH Domain of TAF4 Represses Proliferation and Accelerates Chondrogenic Differentiation of Human Mesenchymal Stem Cells

et al. 2013

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“…Indeed, to date, transfactor-Taf4p interactions are arguably the most frequently observed interactions between DNA binding transfactors and TFIID. Factors Sp1, CREB, RAR, HP1, CBF, RanBPM, simian virus 40 small t antigen, NFAT, AhR, and c-Jun have all been reported to interact with Taf4p (1,6,7,13,18,19,28,32,34,54,68,71,89,94). Given these numerous Taf4p-Taf12p-transfactor interactions, it will be interesting to dissect the molecular details of Rap1p-Tafp binding.…”

Section: Discussionmentioning

confidence: 99%

Yeast TFIID Serves as a Coactivator for Rap1p by Direct Protein-Protein Interaction

Garbett

Tripathi

Cencki

et al. 2007

Molecular and Cellular Biology

127

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In vivo studies have previously shown that Saccharomyces cerevisiae ribosomal protein (RP) gene expression is controlled by the transcription factor repressor activator protein 1 (Rap1p) in a TFIID-dependent fashion. Here we have tested the hypothesis that yeast TFIID serves as a coactivator for RP gene transcription by directly interacting with Rap1p. We have found that purified recombinant Rap1p specifically interacts with purified TFIID in pull-down assays, and we have mapped the domains of Rap1p and subunits of TFIID responsible. In vitro transcription of a UAS RAP1 enhancer-driven reporter gene requires both Rap1p and TFIID and is independent of the Fhl1p-Ifh1p coregulator. UAS RAP1 enhancer-driven transactivation in extracts depleted of both Rap1p and TFIID is efficiently rescued by addition of physiological amounts of these two purified factors but not TATA-binding protein. We conclude that Rap1p and TFIID directly interact and that this interaction contributes importantly to RP gene transcription.Eukaryotic mRNA gene transcription is controlled by the action of modular enhancer-binding transactivators, proteins composed of separable DNA binding domains (DBD) and activation domains (AD). DNA-bound transactivators functionally interact with the mRNA gene transcription machinery, the so-called general transcription factors (GTFs) TFIIA, -B, -D, -E, -F, and -H plus RNA polymerase II (RNAP II), to stimulate formation and/or function of the RNAP II preinitiation complex (PIC) (67). Activators also collaborate with one or more factors termed coactivators, proteins that serve as receptors for the transfactor-AD activation signal. Coactivators link transactivator-enhancer DNA binding to the PIC (43) and can be divided into several classes: those that are chromatin active, the mediator complex, and the individual components of the mRNA gene transcription machinery itself.One of the first and likely rate-limiting steps in mRNA gene transcription is the binding of TFIID to the promoter (36,40,47). TFIID is a multisubunit assembly composed of 15 evolutionarily conserved (86) subunits, the TATA-binding protein (TBP) and 14 TBP-associated factors (TAFs) (72). This GTF displays high-affinity, sequence-specific promoter DNA binding activity. Two classes of yeast mRNA-encoding genes have been defined with respect to TFIID TAF function; the first, which is TAF dependent (TAF dep ), requires TAF function for transcription, while the second and smaller group is TAF independent (TAF ind ) (29,31,45,58,81,92). Both types of genes require TBP for wild-type (WT) levels of transcription, but in the case of the TAF ind genes, TBP appears to be recruited via mechanisms distinct from TFIID (4, 80).When mRNA-encoding genes are monitored for TBP and TAF occupancy by chromatin immunoprecipitation (ChIP) assay, TAF dep genes exhibit higher TAF/TBP occupancy ratios than TAF ind genes (39, 45). Three models for TAF function have been proposed (22, 23): TAFs mediate core promoter recognition; TAFs provide essential catalytic activities tha...

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“…In the past few years, it has become evident that the so-called 'general transcription machinery' is in fact a huge repository of regulatory diversity. We now know that subunits of quasi-universal coregulators, such as TFIID or Mediator, play promoter-, signaling-and cell type-specific functions in gene expression (Chen et al, 1994;Albright and Tjian, 2000;Lemon et al, 2001;Brunkhorst et al, 2004;Mo et al, 2004;van de Peppel et al, 2005;Wang et al, 2005;Zhang et al, 2005;Loncle et al, 2007). In a revised model of transcriptional regulation control, specificity is not only provided by sequence-specific DNA-binding proteins, but also by non-DNA-binding coregulators once thought to be 'generic'.…”

Section: Lessons From Genome-wide Studiesmentioning

confidence: 99%

Mechanisms of regulatory diversity within the p53 transcriptional network

2008

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Novel isoforms of the TFIID subunit TAF4 modulate nuclear receptor-mediated transcriptional activity

Cited by 9 publications

References 134 publications

Alternative Splicing Targeting the hTAF4-TAFH Domain of TAF4 Represses Proliferation and Accelerates Chondrogenic Differentiation of Human Mesenchymal Stem Cells

Alternative Splicing Targeting the hTAF4-TAFH Domain of TAF4 Represses Proliferation and Accelerates Chondrogenic Differentiation of Human Mesenchymal Stem Cells

Yeast TFIID Serves as a Coactivator for Rap1p by Direct Protein-Protein Interaction

Mechanisms of regulatory diversity within the p53 transcriptional network

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