First Author | Tian J | Year | 2016 |
Journal | Proc Natl Acad Sci U S A | Volume | 113 |
Issue | 29 | Pages | 8182-7 |
PubMed ID | 27382175 | Mgi Jnum | J:234400 |
Mgi Id | MGI:5789977 | Doi | 10.1073/pnas.1608987113 |
Citation | Tian J, et al. (2016) Insulin induction of SREBP-1c in rodent liver requires LXRalpha-C/EBPbeta complex. Proc Natl Acad Sci U S A 113(29):8182-7 |
abstractText | Insulin increases lipid synthesis in liver by activating transcription of the gene encoding sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c activates the transcription of all genes necessary for fatty acid synthesis. Insulin induction of SREBP-1c requires LXRalpha, a nuclear receptor. Transcription of SREBP-1c also requires transcription factor C/EBPbeta, but a connection between LXRalpha and C/EBPbeta has not been made. Here we show that LXRalpha and C/EBPbeta form a complex that can be immunoprecipitated from rat liver nuclei. Chromatin immunoprecipitation assays showed that the LXRalpha-C/EBPbeta complex binds to the SREBP-1c promoter in a region that contains two binding sites for LXRalpha and is known to be required for insulin induction. Knockdown of C/EBPbeta in fresh rat hepatocytes or mouse livers in vivo reduces the ability of insulin to increase SREBP-1c mRNA. The LXRalpha-C/EBPbeta complex is bound to the SREBP-1c promoter in the absence or presence of insulin, indicating that insulin acts not by increasing the formation of this complex, but rather by activating it. |