Abstract 458: Role of Heterochromatin Protein 1 Binding Partner 3, HP1BP3, in Cardiomyocyte Stress Response

Abstract

Cardiovascular disease (CVD) is a top cause of mortality and a serious economical burden. While many diseases fall under the umbrella of CVD, they all ultimately lead to heart failure. Little is known how and what epigenetic factors could be involved in cardiomyocytes stress response during such end stage event. The objective of this study is to uncover novel epigenetic proteins that might be nodule regulators of stress genes, to better understand and alter inducted stress pathways. Here, we found Heterochromatin Protein 1 Binding Partner 3, Hp1bp3 , in our single nuclear transcriptomics data set of sham and TAC murine cardiomyocytes. Hp1bp3 was up-regulated in a subset of TAC nuclei (53.8% in TAC versus 18.9% in sham) and appeared to be central in a module of disease-related cardiac genes, suggesting its possible role of stress response regulation. Indeed, a subset of DE genes seemed to be co-regulated with Hp1bp3 only in TAC nuclei amongst other subsets of genes that are not co-regulated. In contrast, stress gene regulation in sham nuclei seemed to not be controlled by Hp1bp3 . These data suggest that Hp1bp3 is unique in diseased nuclei and could be an important regulator of specific stress genes. When we performed the Ingenuity Pathway Analysis, we observed that Hp1bp3 -high TAC nuclei activated many cardioprotective pathways, like hypoxia-handling and ErBB-signaling pathways, suggesting Hp1bp3 was up-regulated to initiate a cardioprotective stress-handling response. Further experiments with a transgenic HL-1 cell line over-expressing Hp1bp3 showed a robust down-regulation of stress genes (Nppb, Myh7) after exposure to hypoxia.