The AF-1 and AF-2 Activating Domains of Retinoic Acid Receptor-  (RAR ) and Their Phosphorylation Are Differentially Involved in Parietal Endodermal Differentiation of F9 Cells and Retinoid-Induced Expression of Target Genes

2000 ◽  
Vol 14 (9) ◽  
pp. 1398-1410 ◽  
Author(s):  
C. Rochette-Egly
Keyword(s):  
Retinoic Acid ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Induced Expression ◽  
F9 Cells ◽  
Acid Receptor ◽  
Endodermal Differentiation

scholarly journals Retinoic Acid Receptor-Dependent, Cell-Autonomous, Endogenous Retinoic Acid Signaling and Its Target Genes in Mouse Collecting Duct Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45725 ◽  
Author(s):  
Yuen Fei Wong ◽  
Patricia D. Wilson ◽  
Robert J. Unwin ◽  
Jill T. Norman ◽  
Matthew Arno ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Collecting Duct ◽  
Retinoic Acid Signaling ◽  
Acid Receptor ◽  
Duct Cells ◽  
Dependent Cell ◽  
Collecting Duct Cells

scholarly journals Retinoic Acid Receptor Isotype Specificity in F9 Teratocarcinoma Stem Cells Results from the Differential Recruitment of Coregulators to Retinoic Acid Response Elements

2007 ◽  
Vol 282 (46) ◽  
pp. 33421-33434 ◽  
Author(s):  
Robert F. Gillespie ◽  
Lorraine J. Gudas
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Response Elements ◽  
Acid Receptor ◽  
Group Protein ◽  
F9 Teratocarcinoma

The retinoic acid receptor (RAR) α, β2, and γ isotypes each regulate specific subsets of target genes in F9 teratocarcinoma stem cells. We used chromatin immunoprecipitation assays to monitor the association of RARγ, retinoic X receptor (RXR) α, and coregulators with the RARβ2, Hoxa1, and Cyp26A1 retinoic acid response elements (RAREs) in F9 wild type and RARα, -β2, and -γ null cells. Additionally we quantitatively monitored expression of the corresponding mRNAs. We demonstrated that the association of RARγ and/or RXRα with a RARE was not sufficient for retinoic acid (RA)-mediated transcription of the corresponding target gene. However, the ability of RARγ and/or RXRα to recruit pCIP (AIB1/ACTR/RAC-3/TRAM-1/SRC-3) and p300 to a RARE did correlate with RA-associated transcription of target mRNAs. Therefore, the specific functions of the RAR isotypes do not manifest at the level of their DNA binding but rather from a differential ability to recruit specific components of the transcriptional machinery. We also demonstrated that RA-mediated displacement of the polycomb group protein SUZ12 from a RARE was inhibited in the absence of RARγ. Thus, transcriptional components of the RAR signaling pathway are specifically required for displacement of SUZ12 from RAREs during RA-mediated differentiation of F9 cells.

scholarly journals The Corepressor CTBP2 Is a Coactivator of Retinoic Acid Receptor/Retinoid X Receptor in Retinoic Acid Signaling

2013 ◽  
Vol 33 (16) ◽  
pp. 3343-3353 ◽  
Author(s):  
Prashanth Kumar Bajpe ◽  
Guus J. J. E. Heynen ◽  
Lorenza Mittempergher ◽  
Wipawadee Grernrum ◽  
Iris A. de Rink ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Rna Interference ◽  
Nuclear Receptor ◽  
Transcriptional Control ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Retinoid X Receptor ◽  
Gene Promoters ◽  
Acid Receptor ◽  
Receptor Complexes

Retinoids play key roles in development, differentiation, and homeostasis through regulation of specific target genes by the retinoic acid receptor/retinoid X receptor (RAR/RXR) nuclear receptor complex. Corepressors and coactivators contribute to its transcriptional control by creating the appropriate chromatin environment, but the precise composition of these nuclear receptor complexes remains to be elucidated. Using an RNA interference-based genetic screen in mouse F9 cells, we identified the transcriptional corepressor CTBP2 (C-terminal binding protein 2) as a coactivator critically required for retinoic acid (RA)-induced transcription.CTBP2suppression by RNA interference confers resistance to RA-induced differentiation in diverse murine and human cells. Mechanistically, we find that CTBP2 associates with RAR/RXR at RA target gene promoters and is essential for their transactivation in response to RA. We show that CTBP2 is indispensable to create a chromatin environment conducive for RAR/RXR-mediated transcription by recruiting the histone acetyltransferase p300. Our data reveal an unexpected function of the corepressor CTBP2 as a coactivator for RAR/RXR in RA signaling.

scholarly journals Recruitment of the Histone Methyltransferase SUV39H1 and Its Role in the Oncogenic Properties of the Leukemia-Associated PML-Retinoic Acid Receptor Fusion Protein

2006 ◽  
Vol 26 (4) ◽  
pp. 1288-1296 ◽  
Author(s):  
Roberta Carbone ◽  
Oronza A. Botrugno ◽  
Simona Ronzoni ◽  
Alessandra Insinga ◽  
Luciano Di Croce ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Fusion Protein ◽  
Fusion Proteins ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Histone Methyltransferase ◽  
Dna Methyltransferases ◽  
Histone Deacetylation ◽  
Leukemic Cells ◽  
Acid Receptor

ABSTRACT Leukemia-associated fusion proteins establish aberrant transcriptional programs, which result in the block of hematopoietic differentiation, a prominent feature of the leukemic phenotype. The dissection of the mechanisms of deregulated transcription by leukemia fusion proteins is therefore critical for the design of tailored antileukemic strategies, aimed at reestablishing the differentiation program of leukemic cells. The acute promyelocytic leukemia (APL)-associated fusion protein PML-retinoic acid receptor (RAR) behaves as an aberrant transcriptional repressor, due to its ability to induce chromatin modifications (histone deacetylation and DNA methylation) and silencing of PML-RAR target genes. Here, we indicate that the ultimate result of PML-RAR action is to impose a heterochromatin-like structure on its target genes, thereby establishing a permanent transcriptional silencing. This effect is mediated by the previously described association of PML-RAR with chromatin-modifying enzymes (histone deacetylases and DNA methyltransferases) and by recruitment of the histone methyltransferase SUV39H1, responsible for trimethylation of lysine 9 of histone H3.

scholarly journals Retinoic Acid Receptor-Mediated Induction of ABCA1 in Macrophages

2003 ◽  
Vol 23 (21) ◽  
pp. 7756-7766 ◽  
Author(s):  
Philippe Costet ◽  
Florent Lalanne ◽  
Marie C. Gerbod-Giannone ◽  
Jennifer R. Molina ◽  
Xuan Fu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Direct Repeat ◽  
Direct Role ◽  
Acid Receptor ◽  
Atp Binding Cassette Transporter ◽  
Abca1 Mrna

ABSTRACT ABCA1, the mutant molecule in Tangier Disease, mediates efflux of cellular cholesterol to apoA-I and is induced by liver X receptor (LXR)/retinoid X receptor (RXR) transcription factors. Retinoic acid receptor (RAR) activators (all-trans-retinoic acid [ATRA] and TTNPB) were found to increase ATP-binding cassette transporter 1 (ABCA1) mRNA and protein in macrophages. In cellular cotransfection assays, RARγ/RXR activated the human ABCA1 promoter, via the same direct repeat 4 (DR4) promoter element as LXR/RXR. Chromatin immunoprecipitation analysis in macrophages confirmed the binding of RARγ/RXR to the ABCA1 promoter DR4 element in the presence of ATRA, with weaker binding of RARα/RXR, and no binding of RARβ/RXR. However, in macrophages from RARγ−/− mice, TTNPB still induced ABCA1, in association with marked upregulation of RARα, suggesting that high levels of RARα can compensate for the absence of RARγ. Dose-response experiments with ATRA in mouse primary macrophages showed that other LXR target genes were weakly induced (ABCG1 and SREBP-1c) or not induced (apoE and LXRα). The more specific RAR activator TTNPB did not induce SREBP-1c in mouse primary macrophages or liver. These studies indicate a direct role of RARγ/RXR in induction of macrophage ABCA1.

scholarly journals Tissue-specific distribution of a novel C-terminal truncation retinoic acid receptor mutant which acts as a negative repressor in a promoter- and cell-type-specific manner.

1995 ◽  
Vol 15 (4) ◽  
pp. 1961-1967 ◽  
Author(s):  
T Matsui ◽  
S Sashihara
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Cell Type ◽  
F9 Cells ◽  
Acid Receptor ◽  
Retinoic Acid Response Element ◽  
Specific Distribution ◽  
Mouse Tissues ◽  
Specific Manner ◽  
Cell Type Specific

A cDNA clone which encodes a truncation form of the gamma subtype of the retinoic acid receptor (RAR gamma) has been isolated. The mutant RAR gamma (RAR gamma Bm382) has lost its 65 C-terminal amino acids, thus truncating a part of the dimerization and activation domains. By using a reverse transcription-coupled PCR technique, it was shown that RAR gamma Bm382 is expressed at different levels in various mouse tissues and that the level of its expression does not correlate with that of normal RAR gamma B. Cotransfection studies revealed that RAR gamma Bm382 acts as a repressor of normal RARs in a promoter- and cell-type-specific manner. Transcription of beta RARE and TREinv promoters was inhibited by RAR gamma Bm382 in both HeLa and F9 cells. Unlike these two promoters, however, RAR gamma Bm382 did not inhibit transcription of the TREpal promoter in HeLa cells but did so in F9 cells. Moreover, while transcription of the lamRARE promoter was inhibited by RAR gamma Bm382 in both HeLa and F9 cells, the inhibition was not observed when F9 cells were induced to differentiate with retinoic acid and dibutyryl cyclic AMP. DNA-binding analysis revealed that RAR gamma Bm382 is able to form a heterodimer with the retinoid X receptor and bind to the different types of retinoic acid response elements with almost the same efficiency as normal RAR. By comparison with effects of other truncation mutants created in vitro, it was suggested that the C-terminal end of the ligand binding domain of RAR is crucial for determining the specificity of transactivation by RAR. Given these observations, we discuss the possibility that protein factors which mediate retinoic acid response element- and cell-type-specific transactivation by RAR are present.

SP1 and NF-Y-Dependent Gene Transactivation Defines a Gain-of-Function for the PML-RARα Oncoprotein.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 743-743
Author(s):  
Sake van Wageningen ◽  
Marleen C. Breems-de Ridder ◽  
Gorica Nikoloski ◽  
Claudia A.J. Erpelinck-Verschueren ◽  
Jeannet Nigten ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Dna Binding ◽  
Acute Promyelocytic Leukemia ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Ectopic Expression ◽  
Promyelocytic Leukemia ◽  
Physical Interaction ◽  
Gain Of Function ◽  
Acid Receptor

Abstract PML-RARa is the product of the chromosomal translocation t(15;17) and is the causative oncogene in more than 98% of the cases of acute promyelocytic leukemia. PML-RARa interferes with the transcription of retinoic acid receptor target genes in a dominant manner, contributing to the transformation of the cells. RARa regulates transcription via heterodimerisation with RXR. PML-RARa can bind as a homodimer to the same sequences as RARa/RXR. At supra-physiological dosis of all-trans retionoic acid (ATRA), the block in differentiation in APL can be overcome. ATRA releases co-repressors from PML-RARa and activates RARa target genes. The ID1 gene is rapidly induced by ATRA in acute promyelocytic leukemia cells. Promoter analysis showed that the ID1 promoter was activated by PML-RARa but, unexpectedly, not by wild type RARa/RXR. Surprisingly, PML-RARa lacking the DNA binding domain could still transactivate the ID1 promoter indicating that transactivation was mediated without direct DNA binding. Promoter deletion studies showed that adjacent NF-Y and SP1 binding sites were essential for this transactivation. A direct physical interaction was shown between PML-RARa and SP1 in vitro and chromatin immunoprecepitation assays confirmed that a complex of PML-RARa/NF-Y/Sp1 is present on the ID1 promoter in vivo. In addition, we found that ectopic expression of PML-RARa induced expression of the endogenous ID1 gene in response to retinoic acid. We propose a novel, gain-of-function model for PML-RARa in which the fusion protein interferes with the transcription of SP1-NF-Y regulated genes. Interference is mediated without DNA-binding, through direct interaction with SP1. This implicates that apart from the previously described deregulation of retinoic acid receptor target genes, PML-RARa may deregulate an additional class of genes that are nomally not regulated by retinoid receptors.

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