Retinoic acid induces TGFβ-dependent autocrine fibroblast growth

Fadloun, Anas; Kobi, Dominique; Delacroix, Laurence; Dembélé, Doulaye; Michel, I.; Lardenois, A.; Tisserand, Johan; Losson, Régine; Mengus, Gabrielle; Davidson, Irwin

doi:10.1038/sj.onc.1210657

Cited by 17 publications

(21 citation statements)

References 49 publications

(54 reference statements)

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“…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). The so-called TafH domain within metazoan Taf4 is responsible for mediating interactions with numerous activators (52); however, yeast Taf4 lacks an obvious TafH domain.…”

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

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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

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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

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“…EMSAs were performed essentially as previously described (15). After electrophoresis, the gels were dried and exposed to autoradiographic film or a PhosphorImager plate.…”

Section: Generation and Culture Of Tagged Rar-expressing Cells Taf4mentioning

confidence: 99%

“…Cell-specific binding of RAR to its cognate elements. We have previously noted that the repertoire of RA-regulated genes in MEFs is significantly different from that observed in other cell types such as F9 or ES cells (15). To examine the basis for this specificity, we generated ES cells in which the genes encoding RAR␣ and RAR␥ were modified by homologous recombination to introduce a TAP tag at the C terminus (Fig.…”

Section: Identification Of Rar Target Genes In Mefs To Identify Rar mentioning

confidence: 99%

“…Transcriptome analysis showed that around 1,000 genes are activated or repressed by RA in these cells. Among the activated genes are TGF-␤ ligands and connective tissue growth factor, which is rapidly induced by RA to induce autocrine growth (15,28). While this study identified the genes and pathways that are activated by RA, we could not discriminate between the direct and indirect targets of the RARs.…”

mentioning

confidence: 91%

“…We have previously shown that RA activates the transforming growth factor beta (TGF-␤) signaling pathway to induce morphological changes and serum-independent autocrine growth of Taf4 lox/Ϫ mouse embryonic fibroblasts (MEFs) (15). Transcriptome analysis showed that around 1,000 genes are activated or repressed by RA in these cells.…”

mentioning

confidence: 99%

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Cell-Specific Interaction of Retinoic Acid Receptors with Target Genes in Mouse Embryonic Fibroblasts and Embryonic Stem Cells

Delacroix

Moutier

Altobelli

et al. 2010

Molecular and Cellular Biology

150

136

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All-trans retinoic acid (RA) induces transforming growth factor beta (TGF-␤)-dependent autocrine growth of mouse embryonic fibroblasts (MEFs). We have used chromatin immunoprecipitation to map 354 RA receptor (RAR) binding loci in MEFs, most of which were similarly occupied by the RAR␣ and RAR␥ receptors. Only a subset of the genes associated with these loci are regulated by RA, among which are several critical components of the TGF-␤ pathway. We also show RAR binding to a novel series of target genes involved in cell cycle regulation, transformation, and metastasis, suggesting new pathways by which RA may regulate proliferation and cancer. Few of the RAR binding loci contained consensus direct-repeat (DR)-type elements. The majority comprised either degenerate DRs or no identifiable DRs but anomalously spaced half sites. Furthermore, we identify 462 RAR target loci in embryonic stem (ES) cells and show that their occupancy is cell type specific. Our results also show that differences in the chromatin landscape regulate the accessibility of a subset of more than 700 identified loci to RARs, thus modulating the repertoire of target genes that can be regulated and the biological effects of RA.

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SMAD3 and SP1/SP3 Transcription Factors Collaborate to Regulate Connective Tissue Growth Factor Gene Expression in Myoblasts in Response to Transforming Growth Factor β

Córdova

Rochard

Riquelme-Guzmán

et al. 2015

J of Cellular Biochemistry

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Fibrotic disorders are characterized by an increase in extracellular matrix protein expression and deposition, Duchene Muscular Dystrophy being one of them. Among the factors that induce fibrosis are Transforming Growth Factor type β (TGF-β) and the matricellular protein Connective Tissue Growth Factor (CTGF/CCN2), the latter being a target of the TGF-β/SMAD signaling pathway and is the responsible for the profibrotic effects of TGF-β. Both CTGF and TGF are increased in tissues affected by fibrosis but little is known about the regulation of the expression of CTGF mediated by TGF-β in muscle cells. By using luciferase reporter assays, site directed mutagenesis and specific inhibitors in C2C12 cells; we described a novel SMAD Binding Element (SBE) located in the 5' UTR region of the CTGF gene important for the TGF-β-mediated expression of CTGF in myoblasts. In addition, our results suggest that additional transcription factor binding sites (TFBS) present in the 5' UTR of the CTGF gene are important for this expression and that SP1/SP3 factors are involved in TGF-β-mediated CTGF expression.

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Retinoic acid induces TGFβ-dependent autocrine fibroblast growth

Cited by 17 publications

References 49 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

Cell-Specific Interaction of Retinoic Acid Receptors with Target Genes in Mouse Embryonic Fibroblasts and Embryonic Stem Cells

SMAD3 and SP1/SP3 Transcription Factors Collaborate to Regulate Connective Tissue Growth Factor Gene Expression in Myoblasts in Response to Transforming Growth Factor β

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