H3K9ac ChIP-seq profiling of wild-type and Slc31a1 conditional knockout mouse bone marrow stromal cells

This study identifies SLC31A1-mediated copper uptake as a cell-intrinsic metabolic checkpoint required for BMSC osteogenic differentiation and skeletal integrity. Mesenchymal lineage-specific Slc31a1 deletion impaired bone formation and BMSC osteogenesis and caused Slc31a1-deficient BMSCs to accumulate in an ID1-high progenitor-like state.

To investigate the epigenetic mechanism underlying this phenotype, H3K9ac ChIP-seq was performed in wild-type and Slc31a1 conditional knockout mouse BMSCs. The analysis revealed increased H3K9ac enrichment in Slc31a1-deficient BMSCs, including enhanced H3K9ac signal at the Id1 locus, supporting a model in which SLC31A1-dependent copper uptake maintains mitochondrial complex IV integrity and NAD+ homeostasis to enable SIRT1-dependent epigenetic repression of Id1 during osteogenic commitment.