Charting the transcriptional regulatory changes in mouse liver during fasting.

Abstract

Summary In a recent paper: Goldstein I, Baek S, Presman DM, Paakinaho V, Swinstead EE, Hager GL. Transcription factor assisted loading and enhancer dynamics dictate the hepatic fasting response. Genome Res. 2017 Mar;27(3):427-39., the authors used a number of functional genomics approaches to explore the transcriptional regulatory dynamics that occur during hepatic fasting. They used chromatin landscape data to identify key fasting-related transcription factors, four of which were further investigated because they are known players of the fasting response: CEBPB (CCAAT enhancer binding-beta), CREB1 (cAMP responsive element binding protein I), GR (glucocorticoid receptor), and PPARA (peroxisome proliferator activated receptor alpha). The authors described two operating modules (GR-CREB1 and PPARA-GR) with synergistic effects driving gluconeogenesis through an assisted loading model and fatty acid oxidation/ketogenesis through a transcription factor cascade, respectively. Finally, using single-cell tracking, they confirmed that GR facilitates CREB1 binding to DNA. This article is protected by copyright. All rights reserved.