The project focuses on investigating how nuclear receptor networks influence metabolism and inflammation (metaflammation) with an emphasis on transcription and epigenomics in the liver. We are focusing in several nuclear receptors and a coregulator called GPS2 (subunit of an HDAC3 corepressor complex), that have been reported to be anti-inflammatory (Fan Nat Med 2016). Based on our in vivo (using GPS2 liver specific knock-out mice) and in vitro (primary hepatocytes, CRISPR-Cas9 mediated GPS2 KO and shRNA mediated GPS2 knocking-down in cell lines) studies, we found GPS2 is involved in fatty acids metabolism, and ablation of GPS2 caused significant changes of fatty acids profile. To specify the mechanism GPS2 plays, microarrays (under normal chow diet and high-fat diet or fed and fasted challenges) and ChIP-seqs (against different transcription factors and histone markers under different challenges) have beed performed to characterize the general changes in transcriptome, cistrome and epigenome, to dissect the dynamic relationship of NRs, GPS2 to other associated co-regulators.