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| Agonist and chemopreventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor |
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| Author(s): Hestermann EV, Brown M |
| Source: MOLECULAR AND CELLULAR BIOLOGY Volume: 23 Issue: 21 Pages: 7920-7925 Published: NOV 2003 |
| Times Cited: 49 References: 35 |
| Abstract: Aryl hydrocarbon receptor (AHR) is a transcription factor whose activity is regulated by environmental agents, including several carcinogenic agonists. We measured recruitment of AHR and associated proteins to the human cytochrome P4501A1 gene promoter in vivo. Upon treatment with the agonist beta-naphthoflavone, AHR is rapidly associated with the promoter and recruits the three members of the p160 family of coactivators as well as the p300 histone acetyltransferase, leading to recruitment of RNA polymerase 11 (Pol 11) and induction of gene transcription. AHR, coactivators, and Pol 11 cycle on and off the promoter, with a period of similar to60 min. In contrast, the chemopreventative AHR ligand 3,3'-diindolylmethane promotes AHR nuclear translocation and p160 coactivator recruitment but, remarkably, fails to recruit Pol II or cause histone acetylation. This novel mechanism of receptor antagonism may account for the antitumor properties of chemopreventative compounds targeting the AHR. |
| Document Type: Article |
| Language: English |
| Reprint Address: Brown, M (reprint author), , 44 Binney St,D730, Boston, MA 02115 USA |
Addresses:
1. Dana Farber Canc Inst, Dept Mol Oncol, Boston, MA 02115 USA
2. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
3. Harvard Univ, Sch Med, Boston, MA 02115 USA |
| Publisher: AMER SOC MICROBIOLOGY, 1752 N ST NW, WASHINGTON, DC 20036-2904 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 734KQ |
| ISSN: 0270-7306 |
| DOI: 10.1128/MCB.23.21.7920-7925.2003 |
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