| First Author | Tzeng J | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 8 | Pages | e0134996 |
| PubMed ID | 26241474 | Mgi Jnum | J:242797 |
| Mgi Id | MGI:5906538 | Doi | 10.1371/journal.pone.0134996 |
| Citation | Tzeng J, et al. (2015) An Ideal PPAR Response Element Bound to and Activated by PPARalpha. PLoS One 10(8):e0134996 |
| abstractText | Peroxisome proliferator-activated receptor-alpha (PPARalpha), a nuclear receptor, plays an important role in the transcription of genes involved in fatty acid metabolism through heterodimerization with the retinoid x receptor (RXR). The consensus sequence of the PPAR response element (PPRE) is composed of two AGGTCA-like sequences directionally aligned with a single nucleotide spacer. PPARalpha and RXR bind to the 5' and 3' hexad sequences, respectively. However, the precise sequence definition of the PPRE remains obscure, and thus, the consensus sequence currently available remains AGGTCANAGGTCA with unknown redundancy. The vague PPRE sequence definition poses an obstacle to understanding how PPARalpha regulates fatty acid metabolism. Here we show that, rather than the generally accepted 6-bp sequence, PPARalpha actually recognized a 12-bp DNA sequence, of which the preferred binding sequence was WAWVTRGGBBAH. Additionally, the optimized RXRalpha hexad binding sequence was RGKTYA. Thus, the optimal PPARalpha/RXRalpha heterodimer binding sequence was WAWVTRGGBBAHRGKTYA. The single nucleotide substitution, which reduces binding of RXRalpha to DNA, attenuated PPARalpha-induced transcriptional activation, but this is not always true for PPARalpha. Using the definition of the PPRE sequence, novel PPREs were successfully identified. Taken altogether, the provided PPRE sequence definition contributes to the understanding of PPARalpha signaling by identifying PPARalpha direct target genes with functional PPARalpha response elements. |
