References of "Davidson, Irwin"
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See detailRetinoic acid receptors recognise the mouse genome through binding elements with diverse spacing and topology
Moutier, Emmanuel; Ye, Tao; Choukrallah, Mohamed-Amin et al

in Journal of Biological Chemistry (2012)

Retinoic Acid Receptors (RARs) heterodimerise with Retinoid X Receptors (RXRs) and bind to RA-response elements (RAREs) in the regulatory regions of their target genes. While previous studies on limited ... [more ▼]

Retinoic Acid Receptors (RARs) heterodimerise with Retinoid X Receptors (RXRs) and bind to RA-response elements (RAREs) in the regulatory regions of their target genes. While previous studies on limited sets of RA-regulated genes have defined canonical RAREs as direct repeats of the consensus RGKTCA separated by 1, 2 or 5 nucleotides (DR1, DR2, DR5), we show that in mouse embryoid bodies or F9 embryonal carcinoma cells, RARs occupy a large repertoire of sites with DR0, DR8 and IR0 (inverted repeat 0) elements. Recombinant RAR-RXR binds these non-canonical spacings in vitro with comparable affinities to DR2 and DR5. Most DR8 elements comprise three half sites with DR2 and DR0 spacings. This specific half site organisation constitutes a previously unrecognised, but frequent signature of RAR binding elements. In functional assays, DR8 and IR0 elements act as independent RAREs, while DR0 does not. Our results reveal an unexpected diversity in the spacing and topology of binding elements for the RAR-RXR heterodimer. The differential ability of RAR-RXR bound to DR0 compared to DR2, DR5 and DR8 to mediate RA-dependent transcriptional activation indicates that half site spacing allosterically regulates RAR function. [less ▲]

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See detailA SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.
Bertolotto, Corine; Lesueur, Fabienne; Giuliano, Sandy et al

in Nature (2011), 480(7375), 94-8

So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus ... [more ▼]

So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (PsiKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer. [less ▲]

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See detailCell-specific interaction of retinoic acid receptors with target genes in mouse embryonic fibroblasts and embryonic stem cells.
Delacroix, Laurence ULg; Moutier, Emmanuel; Altobelli, Gioia et al

in Molecular & Cellular Biology (2010), 30(1), 231-44

All-trans retinoic acid (RA) induces transforming growth factor beta (TGF-beta)-dependent autocrine growth of mouse embryonic fibroblasts (MEFs). We have used chromatin immunoprecipitation to map 354 RA ... [more ▼]

All-trans retinoic acid (RA) induces transforming growth factor beta (TGF-beta)-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 alpha and RAR gamma receptors. Only a subset of the genes associated with these loci are regulated by RA, among which are several critical components of the TGF-beta 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. [less ▲]

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See detailLocalization of human transcription factor TEF-4 and TEF-5 (TEAD2, TEAD3) genes to chromosomes 19q13.3 and 6p21.2 using fluorescence in situ hybridization and radiation hybrid analysis
Jacquemin, Patrick; Depetris, Danielle; Mattei, Marie-Geneviève et al

in Genomics (1999), 55(1), 127-9

Embryonic TEA domain-containing factor (ETF) belongs to the family of proteins structurally related to transcriptional enhancer factor-1 (TEF-1) and is implicated in neural development. Isolation and ... [more ▼]

Embryonic TEA domain-containing factor (ETF) belongs to the family of proteins structurally related to transcriptional enhancer factor-1 (TEF-1) and is implicated in neural development. Isolation and characterization of the cosmid clones encoding the mouse ETF gene (Etdf) revealed thatEtdfspans approximately 17.9 kb and consists of 12 exons. The exon–intron structure ofEtdfclosely resembles that of theDrosophila scallopedgene, indicating that these genes may have evolved from a common ancestor. The multiple transcription initiation sites revealed by S1 protection and primer extension analyses are consistent with the absence of the canonical TATA and CAAT boxes in the 5′-flanking region, which contains many potential regulatory sequences, such as the E-box, N-box, Sp1 element, GATA-1 element, TAATGARAT element, and B2 short interspersed element (SINE) as well as several direct and inverted repeat sequences. TheEtdflocus was assigned to the proximal region of mouse chromosome 7 using fluorescencein situhybridization and linkage mapping analyses. These results provide the molecular basis for studying the regulation,in vivofunction, and evolution ofEtdf. *1 The approved gene symbol for embryonic TEA domain-containing factor (ETF) by MGD isEtdf.The nucleotide sequences reported in this paper have been deposited with the GenBank/EMBL/DDBJ Data Libraries under Accession Nos. D83586–D83596. Mapping data from this article have been deposited in the Mouse Genome Database under Accession Nos. MGD-CREX-618 for genetic mapping and MGD-INEX-21 forin situhybridization, respectively. [less ▲]

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See detailGenomic structure and chromosomal mapping of the mouse transcription factor TEF-5 (Tead3) gene
Jacquemin, Patrick; Chen, Zhi; Martial, Joseph ULg et al

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (1999), 10(6), 632-4

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See detailHuman TEF-5 is preferentially expressed in placenta and binds to multiple functional elements of the human chorionic somatomammotropin-B gene enhancer
Jacquemin, Patrick; Martial, Joseph ULg; Davidson, Irwin

in Journal of Biological Chemistry (1997), 272(20), 12928-37

We report the cloning of a cDNA encoding the human transcription factor hTEF-5, containing the TEA/ATTS DNA binding domain and related to the TEF family of transcription factors. hTEF-5 is expressed in ... [more ▼]

We report the cloning of a cDNA encoding the human transcription factor hTEF-5, containing the TEA/ATTS DNA binding domain and related to the TEF family of transcription factors. hTEF-5 is expressed in skeletal and cardiac muscle, but the strongest expression is observed in the placenta and in placenta-derived JEG-3 choriocarcinoma cells. In correlation with its placental expression, we show that hTEF-5 binds to several functional enhansons of the human chorionic somatomammotropin (hCS)-B gene enhancer. We define a novel functional element in this enhancer comprising tandemly repeated sites to which hTEF-5 binds cooperatively. In the corresponding region of the hCS-A enhancer, which is known to be inactive, this element is inactivated by a naturally occurring single base mutation that disrupts hTEF-5 binding. We further show that the binding of the previously described placental protein f/chorionic somatomammotropin enhancer factor-1 to TEF-binding sites is disrupted by monoclonal antibodies directed against the TEA domain and that this factor is a proteolytic degradation product of the TEF factors. These results strongly suggest that hTEF-5 regulates the activity of the hCS-B gene enhancer. [less ▲]

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See detailA novel family of developmentally regulated mammalian transcription factors containing the TEA/ATTS DNA binding domain
Jacquemin, Patrick; Hwang, Jung-Joo; Martial, Joseph ULg et al

in Journal of Biological Chemistry (1996), 271(36), 21775-85

We describe the molecular cloning of two novel human and murine transcription factors containing the TEA/ATTS DNA binding domain and related to transcriptional enhancer factor-1 (TEF-1). These factors ... [more ▼]

We describe the molecular cloning of two novel human and murine transcription factors containing the TEA/ATTS DNA binding domain and related to transcriptional enhancer factor-1 (TEF-1). These factors bind to the consensus TEA/ATTS cognate binding site exemplified by the GT-IIC and Sph enhansons of the SV40 enhancer but differ in their ability to bind cooperatively to tandemly repeated sites. The human TEFs are differentially expressed in cultured cell lines and the mouse (m)TEFs are differentially expressed in embryonic and extra-embryonic tissues in early post-implantation embryos. Strikingly, at later stages of embryogenesis, mTEF-3 is specifically expressed in skeletal muscle precursors, whereas mTEF-1 is expressed not only in developing skeletal muscle but also in the myocardium. Together with previous data, these results point to important, partially redundant, roles for these TEF proteins in myogenesis and cardiogenesis. In addition, mTEF-1 is strongly coexpressed with mTEF-4 in mitotic neuroblasts, while accentuated mTEF-4 expression is also observed in the gut and the nephrogenic region of the kidney. These observations suggest additional roles for the TEF proteins in central nervous system development and organogenesis. [less ▲]

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