P-88 - Involvement of histone acetylation and methylation in SOD3 regulation in human monocytic THP-1 cells

Abstract

Superoxide dismutase 3 (SOD3), a secretory SOD isozyme, displays a unique and cell-specific expression pattern, and epigenetics plays a critical role in its expression. To date, we have determined that histone acetylation governs phorbol ester (TPA)-elicited SOD3 expression in human monocytic THP-1 cells; however, the molecular mechanisms involving its induction remains unclear. Present data demonstrated that histone deacetylase 1 (HDAC1) and histone acetyltransferase (p300) coordinated SOD3 induction. Moreover, it was determined that myocyte enhancer factor 2 A (MEF2A) and MEF2D function as scaffold proteins, indicating that MEF2/HDAC1 or MEF2/p300 complex regulates SOD3 expression. On the other hand, asymmetric H4R3me2 (H4R3me2a), an epigenetic marker for transcription activation, was also induced in TPA-treated THP-1 cells, suggesting that histone methylation regulates SOD3 expression as well. As expected, our ChIP data clearly showed that the level of H4R3me2a within the proximal SOD3 promoter region was significantly enhanced. Overall, we have found that histone modifications including acetylation and methylation govern SOD3 expression in THP-1 cells.