<b>Identification of BAF60b as a chromatin remodeling checkpoint of diet-induced fatty liver disease</b>

<p dir="ltr"><b>Abstract</b></p><p dir="ltr"><a href="" target="_blank">Overnutrition has gradually become the primary causative factor of nonalcoholic fatty liver disease (NAFLD)</a>. <a href="" target="_blank">However, how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression remains poorly understood.</a> <a href="" target="_blank">Here, we identified hepatic BAF60b as a lipid-sensitive subunit of the switch/sucrose-nonfermentable (SWI/SNF) chromatin-remodeling complex and is negatively associated with liver steatosis in mice and humans. Hepatic BAF60b deficiency promotes high-fat diet (HFD)-induced liver steatosis in mice, while transgenic expression of BAF60b in the liver attenuates HFD-induced obesity and NAFLD, both accompanied by a marked regulation of PPARγ expression. Mechanistically, through motif analysis of liver ATAC-Seq and multiple validation experiments, we identified CCAAT/enhancer‐binding protein β (C/EBPβ) as the transcription factor that interacts with BAF60b to suppress PPARγ gene expression, thereby controlling hepatic lipid accumulation and NAFLD progression.</a> This work uncovers <a href="" target="_blank">hepatic BAF60b as a negative regulator of liver steatosis through C/EBPβ dependent chromatin remodeling.</a></p><p dir="ltr"><b>Keyword</b><b>：</b>SWI/SNF complex; BAF60b; NAFLD; Transcriptional regulation</p><p dir="ltr"><b>Article Highlights</b></p><p dir="ltr">• We aim to understand how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression.</p><p dir="ltr">• Hepatic BAF60b is a dietary-lipid sensor and is negatively associated with liver steatosis. We used liver-specific BAF60b knockout and transgenic mice, combining with multi-omics techniques, to study the role of BAF60b in NAFLD progression.</p><p dir="ltr">• Our findings uncover BAF60b as a key chromatin remodeling checkpoint factor in controlling hepatic lipid sensing, accumulation, and NAFLD progression through engaging the C/EBPβ/PPARγ axis.</p>