Regulating Liver Transcriptional Networks by Endocrine, Extracellular, and Intrinsic Cues

The liver is central to various systemic functions, and liver failure, fatal. The liver is responsible for generating lipid and carbohydrate reservoirs following feeding and the production of alternative fuels during fasting. It produces and secretes bile acids as well as acute phase reactants, regulates iron and cholesterol homeostasis, and detoxifies drugs. A large body of data is available to show that many of these functions are regulated by dynamic hepatic gene expression patterns. Several reports show that extracellular cues (e.g. hormones, cytokines) and intrinsic molecular clocks impact hepatic transcriptional networks, including genome-wide regulation of chromatin accessibility and transcription factor occupancy. These discoveries were made possible by high-throughput technologies that enabled the genome-wide characterization of transcriptomics (via RNA-seq), transcription factor binding patterns, histone modification status (ChIP-seq), chromatin accessibility (DNase-seq, ATAC-seq) as well as higher order chromatin structures (4C, Hi-C and ChIA-PET). However, the global effect of many liver-related cues on gene expression and chromatin parameters is not known. Characterizing the effect of these cues on liver cells is paramount to understand how the liver operates to ensure homeostasis and to identify central molecular entities causing liver disease. In addition to characterization, there is an urgent need to address the mechanisms by which transcription factors and other chromatin-regulatory proteins cooperate to elicit a coherent and effective response to extracellular cues. Moreover, emerging technologies enable assessment of cell-to-cell variability via single-cell analyses, deepening our understanding of an integrated response of a population of cells with many sub-populations that contribute differently to the final outcome.

This Research Topic aims to further our understanding of transcriptional and chromatin regulation in liver cells following endocrine, cytokine, metabolite, xenobiotic and other extracellular cues as well as regulators of intrinsic molecular networks. We are looking for Research, Review, and Methods articles dealing with the chromatin and transcriptional aspect of hepatic features. These include, but are not limited to: energy metabolism, nutritional status (fed vs. fasted), diet composition (high-fat diet, low-protein diet etc.), steroid and peptide hormone response, iron homeostasis, circadian clock, drug detoxification, cholesterol and lipoprotein biology, hepatokine production and secretion and acute-phase response. We also welcome articles tackling dysregulation of gene expression in pathologies such as obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), drug-induced liver toxicity, liver cancer, chronic inflammation and more. Lastly, articles describing novel methods or analyses that help tackle issues relating to hepatic regulation of transcription and chromatin states are also welcome.