Nuclear Myosin 1 links genomic architecture to adipose tissue remodeling, metabolic inflammation and obesity in mice

Nuclear myosin 1c (NM1) is a chromatin-associated motor protein with known roles in transcriptional regulation and metabolic control. However, its involvement in adipogenesis and adipose tissue remodeling remains unexplored. Here, we demonstrate that NM1 is a critical regulator of adipocyte differentiation and visceral fat homeostasis. Using an NM1 knockout (KO) mouse model, we observed increased adipose tissue mass, adipocyte hypertrophy, and impaired adipogenic differentiation in mesenchymal stem cell–derived adipocytes ex vivo. Integrative analysis of RNA-seq and ATAC-seq data from wild-type (WT) and NM1 KO mouse embryonic fibroblasts (MEFs) revealed a subset of genes with concordant changes in transcription and chromatin accessibility, many of which are involved in lipid metabolism and adipogenic regulation, including Insig1, Mylip, Lipg, and Fat1. Gene regulatory network modeling using single-cell RNA-seq and TF motif data identified 19 transcription factors (TFs) dysregulated in NM1 KO cells, eight of which (E2f8, Foxo3, Klf6, Npas4, Smad5, Zeb2, Gata4, and Tbx2) also showed significant alterations in chromatin accessibility. Hi-C–based chromatin compartment analysis revealed switching in several adipogenesis-linked genes (Ncoa2, Prdm14, Cops5) in the absence of NM1, suggesting broader effects on 3D genome organization. Together, these findings establish NM1 as a central chromatin-regulatory node that integrates transcription factor activity, enhancer accessibility, and higher-order genome architecture to control adipogenic differentiation. Our results position NM1 and its human paralog MYO1C as potential regulators of obesity and targets for metabolic disease intervention.