| First Author | Ramadoss P | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 3 | Pages | 1313-28 |
| PubMed ID | 24288132 | Mgi Jnum | J:317938 |
| Mgi Id | MGI:6830146 | Doi | 10.1074/jbc.M113.521450 |
| Citation | Ramadoss P, et al. (2014) Novel mechanism of positive versus negative regulation by thyroid hormone receptor beta1 (TRbeta1) identified by genome-wide profiling of binding sites in mouse liver. J Biol Chem 289(3):1313-28 |
| abstractText | Triiodothyronine (T3) regulates key metabolic processes in the liver through the thyroid hormone receptor, TRbeta1. However, the number of known target genes directly regulated by TRbeta1 is limited, and the mechanisms by which positive and especially negative transcriptional regulation occur are not well understood. To characterize the TRbeta1 cistrome in vivo, we expressed a biotinylated TRbeta1 in hypo- and hyperthyroid mouse livers, used ChIP-seq to identify genomic TRbeta1 targets, and correlated these data with gene expression changes. As with other nuclear receptors, the majority of TRbeta1 binding sites were not in proximal promoters but in the gene body of known genes. Remarkably, T3 can dictate changes in TRbeta1 binding, with strong correlation to T3-induced gene expression changes, suggesting that differential TRbeta1 binding regulates transcriptional outcome. Additionally, DR-4 and DR-0 motifs were significantly enriched at binding sites where T3 induced an increase or decrease in TRbeta1 binding, respectively, leading to either positive or negative regulation by T3. Taken together, the results of this study provide new insights into the mechanisms of transcriptional regulation by TRbeta1 in vivo. |
