HMGN3 ChIP-seq in AC16 cells and Bulk-RNAseq in AC16 cell with and without HMGN3 knockdown

Chromatin structure plays a central role in regulating gene expression and maintaining cellular identity, yet the structural factors driving these processes in cardiac disease remain poorly defined. To investigate whether these factors can distinguish healthy from diseased cardiac cell populations, we generated a comprehensive list of chromatin structural genes based on an extensive literature review. Applying this list to a published single-cell RNA sequencing (scRNA-seq) dataset from human hearts with and without dilated cardiomyopathy (DCM), we found that chromatin structural gene expression effectively stratified cardiomyocyte and fibroblast populations by disease status. Diseased cardiomyocytes exhibited reduced expression of contractile genes and increased expression of cardiomyopathy markers, while fibroblasts showed enhanced activation signatures. Among these factors, HMGN3 emerged as a candidate of interest, showing consistent downregulation in cardiomyocytes from human patients, as well as in mouse (pressure overload) and pig (myocardial infarction) models of heart failure. Functional studies in AC16 cells revealed that HMGN3 depletion reduced proliferation, increased apoptosis, and decreased active chromatin marks (H3K27ac, H3K4me1), accompanied by increased chromatin compaction. These findings identify HMGN3 as a potential regulator of chromatin architecture in diseased cardiomyocytes, highlight the utility of chromatin structural gene expression in distinguishing pathological cardiac states, and reinforce the role of chromatin organization in shaping the cardiac phenotype. In this dataset, HMGN3 ChIP-seq and Bulk-RNAseq data with and without HMGN3 knockdown were generated using AC16 cells.