Yanyan Zhao
Shengjing Hospital of China Medical University, China
Title: Nkx2.5 regulates Nsd1 in response to oxidative stress in cardiac muscle cells
Biography
Biography: Yanyan Zhao
Abstract
Nuclear receptor-binding SET domain-containing protein 1 (Nsd1) is a histone lysine methyltransferase, and the effect of NSD1 in response to oxidative stress in cardiac muscle cells remains poorly understood. Current study demonstrated that the protein and mRNA levels of NSD1 was reduced by H2O2 in H9C2 cells. We analyzed the promoter of NSD1 gene, predicted an NK2 transcription factor related locus 5 (Nkx2.5) binding element (NKE) at position -412/-406 in the NSD1 promoter, and confirmed it by an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay. Luciferase activity analysis indicated H2O2 decreased the p646-luc promoter activity, and Nkx2.5-specific siRNA weakened H2O2 inhibition on the p646-luc promoter. However, H2O2 did not affected mutant NKE promoter p646-luc-mut compared with wild p646-luc promoter. Furthermore, overexpression and depletion of Nkx2.5 led to the increase and decrease of NSD1 protein and mRNA levels in H9C2 cells. In addition, Nkx2.5 was downregulated by H2O2. Therefore we hypothesized that oxidative stress reduced NSD1 expression through suppression of Nkx2.5, and we going to focus on the alteration of histone methylation of NSD in response oxidative stress in future study.