Unknown,Transcriptomics,Genomics,Proteomics

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Examination of hepatic SREBP-2 binding using ChIP-Seq


ABSTRACT: Sterol regulatory element binding proteins (SREBPs) are key transcriptional regulators of lipid metabolism. To define functional differences between the three mammalian SREBPs we are using 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 hepatic SREBP-2 binds preferentially to two different gene-proximal motifs. Gene ontology analyses suggests SREBP-2 targets lipid metabolic processes as expected but apoptosis and autophagy gene categories were also enriched. We show 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. Examination of hepatic SREBP-2 binding using ChIP-Seq. One ChIP-Seq dataset and one IgG control.

ORGANISM(S): Mus musculus

SUBMITTER: Jacob Biesinger 

PROVIDER: E-GEOD-28082 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.

Seo Young-Kyo YK   Jeon Tae-Il TI   Chong Hansook Kim HK   Biesinger Jacob J   Xie Xiaohui X   Osborne Timothy F TF  

Cell metabolism 20110401 4


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 target  ...[more]

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