Details

Autor(en) / Beteiligte

• Cebola, Inês

Titel

Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

Ist Teil von

• Wiley interdisciplinary reviews. Mechanisms of disease, 2020-05, Vol.12 (3), p.e1480-n/a

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2020

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) result from complex interactions between intrinsic and extrinsic factors, including genetics and exposure to obesogenic environments. These risk factors converge in aberrant gene expression patterns in the liver, which are underlined by altered cis‐regulatory networks. In homeostasis and in disease states, liver cis‐regulatory networks are established by coordinated action of liver‐enriched transcription factors (TFs), which define enhancer landscapes, activating broad gene programs with spatiotemporal resolution. Recent advances in DNA sequencing have dramatically expanded our ability to map active transcripts, enhancers and TF cistromes, and to define the 3D chromatin topology that contains these elements. Deployment of these technologies has allowed investigation of the molecular processes that regulate liver development and metabolic homeostasis. Moreover, genomic studies of NAFLD patients and NAFLD models have demonstrated that the liver undergoes pervasive regulatory rewiring in NAFLD, which is reflected by aberrant gene expression profiles. We have therefore achieved an unprecedented level of detail in the understanding of liver cis‐regulatory networks, particularly in physiological conditions. Future studies should aim to map active regulatory elements with added levels of resolution, addressing how the chromatin landscapes of different cell lineages contribute to and are altered in NAFLD and NAFLD‐associated metabolic states. Such efforts would provide additional clues into the molecular factors that trigger this disease. This article is categorized under: Biological Mechanisms > Metabolism Biological Mechanisms > Regulatory Biology Laboratory Methods and Technologies > Genetic/Genomic Methods Complex gene regulatory networks underlie liver homeostasis. NAFLD development is characterized by changes gene expression, which reflect pervasive rewiring of liver transcriptional networks by integration of aberrant intrinsic and extrinsic cues.