| First Author | Zhan Q | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 11 | Pages | e50013 |
| PubMed ID | 23166811 | Mgi Jnum | J:195015 |
| Mgi Id | MGI:5475436 | Doi | 10.1371/journal.pone.0050013 |
| Citation | Zhan Q, et al. (2012) Function annotation of hepatic retinoid x receptor alpha based on genome-wide DNA binding and transcriptome profiling. PLoS One 7(11):e50013 |
| abstractText | BACKGROUND: Retinoid x receptor alpha (RXRalpha) is abundantly expressed in the liver and is essential for the function of other nuclear receptors. Using chromatin immunoprecipitation sequencing and mRNA profiling data generated from wild type and RXRalpha-null mouse livers, the current study identifies the bona-fide hepatic RXRalpha targets and biological pathways. In addition, based on binding and motif analysis, the molecular mechanism by which RXRalpha regulates hepatic genes is elucidated in a high-throughput manner. PRINCIPAL FINDINGS: Close to 80% of hepatic expressed genes were bound by RXRalpha, while 16% were expressed in an RXRalpha-dependent manner. Motif analysis predicted direct repeat with a spacer of one nucleotide as the most prevalent RXRalpha binding site. Many of the 500 strongest binding motifs overlapped with the binding motif of specific protein 1. Biological functional analysis of RXRalpha-dependent genes revealed that hepatic RXRalpha deficiency mainly resulted in up-regulation of steroid and cholesterol biosynthesis-related genes and down-regulation of translation- as well as anti-apoptosis-related genes. Furthermore, RXRalpha bound to many genes that encode nuclear receptors and their cofactors suggesting the central role of RXRalpha in regulating nuclear receptor-mediated pathways. CONCLUSIONS: This study establishes the relationship between RXRalpha DNA binding and hepatic gene expression. RXRalpha binds extensively to the mouse genome. However, DNA binding does not necessarily affect the basal mRNA level. In addition to metabolism, RXRalpha dictates the expression of genes that regulate RNA processing, translation, and protein folding illustrating the novel roles of hepatic RXRalpha in post-transcriptional regulation. |
