| First Author | Seo YK | Year | 2011 |
| Journal | Cell Metab | Volume | 13 |
| Issue | 4 | Pages | 367-375 |
| PubMed ID | 21459322 | Mgi Jnum | J:172249 |
| Mgi Id | MGI:5005040 | Doi | 10.1016/j.cmet.2011.03.005 |
| Citation | Seo YK, et al. (2011) Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy. Cell Metab 13(4):367-75 |
| abstractText | Sterol regulatory element-binding proteins (SREBPs) are key transcriptional regulators of lipid metabolism. To define functional differences between the three mammalian SREBPs we used genome-wide ChIP-seq with isoform-specific antibodies and chromatin from select tissues of mice challenged with different dietary conditions that enrich for specific SREBPs. We show that hepatic SREBP-2 binds preferentially to two different gene-proximal motifs. A Gene Ontology (GO) analysis suggests SREBP-2 targets lipid metabolic processes as expected, but apoptosis and autophagy gene categories were also enriched. We show that SREBP-2 directly activates autophagy genes during cell-sterol depletion, conditions known to induce both autophagy and nuclear SREBP-2 levels. Additionally, SREBP-2 knockdown during nutrient depletion decreased autophagosome formation and lipid droplet association of the autophagosome targeting protein LC3. Thus, the lipid droplet could be viewed as a third source of cellular cholesterol, which along with sterol synthesis and uptake, is also regulated by SREBP-2. |
