Histone Lysine Methylation in TGF-β1 Mediated p21 Gene Expression in Rat Mesangial Cells. (9th May 2016)

• Record Type: Journal Article
• Authors: Guo, Qiaoyan; Li, Xiaoxia; Han, Hongbo; Li, Chaoyuan; Liu, Shujun; Gao, Wenhui; Sun, Guangdong
• Other Names: Zheng Yujungeorge Academic Editor.
• Is Part Of: BioMed research international. Volume 2016(2016)
• Publication Date: 2016-05-09
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2016/6927234
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : Transforming growth factor beta1- (TGF- β 1-) induced p21-dependent mesangial cell (MC) hypertrophy plays a key role in the pathogenesis of chronic renal diseases including diabetic nephropathy (DN). Increasing evidence demonstrated the role of posttranscriptional modifications (PTMs) in the event; however, the precise regulatory mechanism of histone lysine methylation remains largely unknown. Here, we examined the roles of both histone H3 lysine 4 and lysine 9 methylations (H3K4me/H3K9me) in TGF- β 1 induced p21 gene expression in rat mesangial cells (RMCs). Our results indicated that TGF- β 1 upregulated the expression of p21 gene in RMCs, which was positively correlated with the increased chromatin marks associated with active genes (H3K4me1/H3K4me2/H3K4me3) and negatively correlated with the decreased levels of repressive marks (H3K9me2/H3K9me3) at p21 gene promoter. TGF- β 1 also elevated the recruitment of the H3K4 methyltransferase (HMT) SET7/9 to the p21 gene promoter. SET7/9 gene silencing with small interfering RNAs (siRNAs) significantly abolished the TGF- β 1 induced p21 gene expression. Taken together, these results reveal the key role of histone H3Kme in TGF- β 1 mediated p21 gene expression in RMC, partly through HMT SET7/9 occupancy, suggesting H3Kme and SET7/9 may be potential renoprotective agents in managing chronic renal diseases.