Hormone-controlled cooperative binding of transcription factors drives synergistic induction of fasting-regulated genes.

ABSTRACT: During fasting, hepatocytes produce glucose in response to hormonal signals. Glucagon and glucocorticoids are principal fasting hormones that cooperate in regulating glucose production via gluconeogenesis. However, how these hormone signals are integrated and interpreted to a biological output is unknown. Here, we use genome-wide profiling of gene expression, enhancer dynamics and transcription factor (TF) binding in primary mouse hepatocytes to uncover the mode of cooperation between glucagon and glucocorticoids. We found that compared to a single treatment with each hormone, a dual treatment directs hepatocytes to a pro-gluconeogenic gene program by synergistically inducing gluconeogenic genes. The cooperative mechanism driving synergistic gene expression is based on 'assisted loading' w

SUBMITTER: Goldberg D 

PROVIDER: S-EPMC9177981 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature