RAR-mediated epigenetic control of the cytochrome P450 Cyp26a1 in embryocarcinoma cells

Pozzi, Silvia; Rossetti, Stefano; Bistulfi, Gaia; Sacchi, Nicoletta

doi:10.1038/sj.onc.1209173

Cited by 34 publications

(29 citation statements)

References 26 publications

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“…We found recently that RARa, via RARb2, controls the transcription of another RAresponsive gene, CYP26A1, an enzyme implicated in RA catabolism and neural morphogenesis (ref. 30 and references within). Thus, RA-RARa signal seems to control, through a concerted epigenetic mechanism, at least two RA-responsive genes involved in retinol/ RA metabolism as well as morphogenesis.…”

Section: Discussionmentioning

confidence: 99%

A Repressive Epigenetic Domino Effect Confers Susceptibility to Breast Epithelial Cell Transformation: Implications for Predicting Breast Cancer Risk

Bistulfi

Pozzi

Ren³

et al. 2006

Cancer Research

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Retinoic acid (RA) is a master epigenetic regulator that plays a pivotal role in both breast morphogenesis and development. Here, we show for the first time that RA, via the RA receptor A (RARA), epigenetically regulates in a concerted fashion the transcription of two RA-responsive genes, the RA receptor B2 (RARb2) and the cellular retinol-binding protein 1 (CRBP1). Specifically, an impaired RA signal through RARA in human breast epithelial cells triggers a repressive epigenetic domino effect, involving first RARb2 and second CRBP1. The phenotype acquired by breast epithelial cells clearly implies that the resistance to RA-mediated growth inhibition precedes the acquisition of morphological epithelial transformation, thus supporting the occurrence of sequential transcriptional silencing of first RARb2 and second CRBP1. The identification of this epigenetic network mechanistically linking RARb2 and CRBP1 transcription provides the basis for devising more accurate epigenetic tests for the prediction of breast cancer risk.

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Section: Discussionmentioning

confidence: 99%

A Repressive Epigenetic Domino Effect Confers Susceptibility to Breast Epithelial Cell Transformation: Implications for Predicting Breast Cancer Risk

Bistulfi

Pozzi

Ren³

et al. 2006

Cancer Research

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“…at ASPET Journals on May 10, 2018 molpharm.aspetjournals.org ously in promyelocytic leukemia cells, embryocarcinoma cells, and intestinal cells (Lampen et al, 2001a;Ozpolat et al, 2002;Idres et al, 2005;Pozzi et al, 2006). In contrast, in mouse F9 cells, RAR␥ was shown to regulate CYP26A1 gene expression, because CYP26A1 induction was lost in RAR␥(Ϫ/Ϫ) cell lines (Abu-Abed et al, 1998).…”

mentioning

confidence: 99%

A Comparison of the Roles of Peroxisome Proliferator-Activated Receptor and Retinoic Acid Receptor on CYP26 Regulation

et al. 2009

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The cytochrome P450 26 family is believed to be responsible for all-trans-retinoic acid (atRA) metabolism and elimination in the human fetus and adults. CYP26A1 and CYP26B1 mRNA is expressed in a tissue-specific manner, and mice in which the CPY26 isoform has been knocked out show distinct malformations and lethality. The aim of this study was to determine differences in CYP26A1 and CYP26B1 regulation and expression. Analysis of CYP26A1 and CYP26B1 expression in a panel of 57 human livers showed CYP26A1 to be the major CYP26 isoform present in the liver, and its expression to be subject to large interindividual variability between donors. CYP26A1 and retinoic acid receptor (RAR) ␤ were found to be greatly inducible by atRA in HepG2 cells, whereas CYP26B1, RAR␣, and RAR␥ were induced to a much lesser extent. Based on treatments with RAR isoform-selective ligands, RAR␣ is the major isoform responsible for CYP26A1 and RAR␤ induction in HepG2 cells. Classic cytochrome P450 inducers did not affect CYP26 transcription, whereas the peroxisome proliferator-activated receptor (PPAR) ␥ agonists pioglitazone and rosiglitazone up-regulated CYP26B1 transcription by as much as 209-Ϯ 80-fold and CYP26A1 by 10-fold. RAR␤ was also up-regulated by pioglitazone and rosiglitazone. CYP26B1 induction by PPAR␥ agonists was abolished by the irreversible PPAR␥ antagonist 2-chloro-5-nitrobenzanilide (GW9662), whereas RAR␤ and CYP26A1 induction was unaffected by GW9662. Overall, the results of this study suggest that CYP26B1 and CYP26A1 are regulated by different nuclear receptors, resulting in tissue-specific expression patterns. The fact that drugs can alter the expression of CYP26 enzymes may have toxicological and therapeutic importance.

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“…If RAs can directly influence DNMT levels, this would represent another retinoid-regulated epigenetic mechanism to establish heritable DNA methylation patterns. However, not all epigenetic mechanisms influenced by RA involve DNA methylation (Pozzi et al, 2006; see also next set of references). In general, HDA and other chromatin-modifying enzymes (both RNA and protein based) may be recruited to specific DNA methylation "patterns," thereby contributing to a relatively stable, heritable chromatin structure.…”

Section: Retinoids and Epigenetic Mechanismsmentioning

confidence: 99%

“…Many epigenetic mechanisms may rely fundamentally on establishing, removing, or otherwise changing DNA methylation patterns (see Section 14.3). In terms of the commonly discussed relation between DNA methylation and suppression of gene transcription, however, it is important to note that DNA methylation may not be a requirement for all types of transcriptional silencing (e.g., Milutinovic et al, 2000;Pozzi et al, 2006;Zhang et al, 2007).…”

Section: Retinoids and Epigenetic Mechanismsmentioning

confidence: 99%

Epigenetic Regulation by Retinoids

Vieira¹

2011

Nutrition in Epigenetics

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RAR-mediated epigenetic control of the cytochrome P450 Cyp26a1 in embryocarcinoma cells

Cited by 34 publications

References 26 publications

A Repressive Epigenetic Domino Effect Confers Susceptibility to Breast Epithelial Cell Transformation: Implications for Predicting Breast Cancer Risk

A Repressive Epigenetic Domino Effect Confers Susceptibility to Breast Epithelial Cell Transformation: Implications for Predicting Breast Cancer Risk

A Comparison of the Roles of Peroxisome Proliferator-Activated Receptor and Retinoic Acid Receptor on CYP26 Regulation

Epigenetic Regulation by Retinoids

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