| First Author | Takeda Y | Year | 2011 |
| Journal | Nucleic Acids Res | Volume | 39 |
| Issue | 11 | Pages | 4769-82 |
| PubMed ID | 21317191 | Mgi Jnum | J:173696 |
| Mgi Id | MGI:5050025 | Doi | 10.1093/nar/gkq1335 |
| Citation | Takeda Y, et al. (2011) Retinoic acid-related orphan receptor {gamma} directly regulates neuronal PAS domain protein 2 transcription in vivo. Nucleic Acids Res 39(11):4769-82 |
| abstractText | Retinoic acid-related orphan receptors (RORs) and the basic helix-loop-helix-PAS transcription factor Npas2 have been implicated in the control of circadian rhythm. In this study, we demonstrate that RORgamma directly regulates Npas2 expression in vivo. Although the rhythmicity of Npas2 mRNA expression was maintained in RORgamma(-/-) mice, the peak level of expression was significantly reduced in several tissues, while loss of RORalpha had little effect. Inversely, overexpression of RORgamma in hepatoma Hepa1-6 cells greatly induced the expression of Npas2. RORgamma-activated Npas2 transcription directly by binding two ROREs in its proximal promoter. ChIP analysis demonstrated that RORgamma was recruited to this promoter in the liver of wild-type mice, but not RORgamma-deficient mice. Activation of Npas2 correlated positively with chromatin accessibility and level of H3K9 acetylation. The activation of Npas2 by RORgamma was repressed by co-expression with Rev-Erbalpha or addition of the ROR inverse agonist T0901317. Npas2 expression was also significantly enhanced during brown adipose differentiation and that this induction was greatly suppressed in adipose cells lacking RORgamma. Our results indicate that RORgamma and Rev-Erbalpha are part of a feed-back loop that regulates the circadian expression of Npas2 suggesting a regulatory role for these receptors in Npas2-dependent physiological processes. |
