title: Histone Lysine Methylation in TGF-β1 Mediated p21 Gene Expression in Rat Mesangial Cells.
abstract: Transforming growth factor beta1- (TGF-β1-) 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-β1 induced p21 gene expression in rat mesangial cells (RMCs). Our results indicated that TGF-β1 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-β1 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-β1 induced p21 gene expression. Taken together, these results reveal the key role of histone H3Kme in TGF-β1 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.
authors.affiliation: Department of Nephrology, 2nd Hospital of Jilin University, Changchun 130041, China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Nephrology, 2nd Hospital of Jilin University, Changchun 130041, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Endocrinology, 208th Hospital of Chinese PLA, Changchun 130062, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Nephrology, 2nd Hospital of Jilin University, Changchun 130041, China.
authors.forename: Chaoyuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Nephrology, 2nd Hospital of Jilin University, Changchun 130041, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neonatology, 2nd Hospital of Jilin University, Changchun 130041, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Nephrology, 2nd Hospital of Jilin University, Changchun 130041, China.
authors.forename: Guangdong
authors.identifier: 0000-0002-2899-7899
authors.initials: G
authors.lastname: Sun
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006657:Histones / Q000235:genetics*; D008239:Lysine / Q000235:genetics*; D008297:Male; D050527:Mesangial Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D053773:Transforming Growth Factor beta1; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine