Journal
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 51, 2011
Volume 51, Issue -, Pages 75-97Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010510-100605
Keywords
gene regulation; transcription factor; chromatin remodeling; neuronal differentiation; retinoic acid
Categories
Funding
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK060521, R01DK054733] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K02DA013926, R56DA000564, P50DA011806, R01DA000564, R37DA001583, R01DA011190, R01DA001583, K05DA070554] Funding Source: NIH RePORTER
- NIDA NIH HHS [K05 DA070554, DA00564, DA01583, R01 DA000564, P50 DA011806, R01 DA001583, K02-DA13926, R01 DA011190, K02 DA013926, DA11190, K05-DA70554, DA11806, R56 DA000564] Funding Source: Medline
- NIDDK NIH HHS [R01 DK060521, DK54733, DK60521, R01 DK054733] Funding Source: Medline
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Three opioid receptors (ORs) are known: p. opioid receptors (MORs), delta opioid receptors (DORs), and K opioid receptors (KORs). Each is encoded by a distinct gene, and the three OR genes share a highly conserved genomic structure and promoter features, including an absence of TATA boxes and sensitivity to extracellular stimuli and epigenetic regulation. However, each of the genes is differentially expressed. Transcriptional regulation engages both basal and regulated transcriptional machineries and employs activating and silencing mechanisms. In retinoic acid-induced neuronal differentiation, the opioid receptor genes undergo drastically different chromatin remodeling processes and display varied patterns of epigenetic marks. Regulation of KOR expression is distinctly complex, and KOR exerts a unique function in neurite extension, indicating that KOR is not simply a pharmacological cousin of MOR and DOR. As the expression of OR proteins is ultimately controlled by extensive posttranscriptional processing, the pharmacological implication of OR gene regulation at the transcriptional level remains to be determined.
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