@article {1503162,
	title = {Insulin Receptor Associates with Promoters Genome-wide and Regulates Gene Expression},
	journal = {Cell},
	volume = {177},
	number = {3},
	year = {2019},
	month = {2019 04 18},
	pages = {722-736.e22},
	abstract = {Insulin receptor (IR) signaling is central to normal metabolic control and dysregulated in prevalent chronic diseases. IR binds insulin at the cell surface and transduces rapid signaling via cytoplasmic kinases. However, mechanisms mediating long-term effects of insulin remain unclear. Here, we show that IR associates with RNA polymerase II in the nucleus, with striking enrichment at promoters genome-wide. The target genes were highly enriched for insulin-related functions including lipid metabolism and protein synthesis and diseases including diabetes, neurodegeneration, and cancer. IR chromatin binding was increased by insulin and impaired in an insulin-resistant disease model. Promoter binding by IR was mediated by coregulator host cell factor-1 (HCF-1) and transcription factors, revealing an HCF-1-dependent pathway for gene regulation by insulin. These results show that IR interacts with transcriptional machinery at promoters and identify a pathway regulating genes linked to insulin{\textquoteright}s effects in physiology and disease.},
	keywords = {Animals, Cell Line, Tumor, Chromatin, Gene Expression Regulation, Genome-Wide Association Study, Host Cell Factor C1, Humans, Insulin, Liver, Male, Mice, Mice, Inbred C57BL, Promoter Regions, Genetic, Protein Binding, Protein Subunits, Receptor, Insulin, RNA Interference, RNA Polymerase II, RNA, Small Interfering, Signal Transduction},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2019.02.030},
	author = {Hancock, Melissa L and Meyer, Rebecca C and Mistry, Meeta and Khetani, Radhika S and Wagschal, Alexandre and Shin, Taehwan and Ho Sui, Shannan J and N{\"a}{\"a}r, Anders M and Flanagan, John G}
}
