title: Acetylation of Ets-1 is the key to chromatin remodeling for miR-192 expression.
abstract: By regulating gene expression, microRNAs (miRNAs) play pivotal roles in physiological and pathological processes. However, the regulation of miRNAs is elusive. miR-192 is a key regulator of renal fibrosis and hypertrophy in diabetic nephropathy. Natarajan et al. showed that the miR-192 gene contains an upstream region with Ets-1 and Smad3 binding sites. In control cells, all Ets-1 sites were occupied, resulting in a locked chromatin structure that kept miR-192 expression low. In response to transforming growth factor-β (TGF-β) stimulation, Smad3 and Akt were activated, and the latter further activated p300 to induce partial acetylation and dissociation of Ets-1 and the recruitment of Smad3 to the miR-192 gene, inducing transient miR-192 expression. During prolonged TGF-β treatment, p300 acetylated histone and Ets-1, resulting in complete dissociation of Ets-1 and the opening of the chromatin for sustained miR-192 expression. Thus, transcription factors and chromatin remodeling control microRNA gene expression in a dynamic, coordinated fashion.
authors.affiliation: Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. zdong@gru.edu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000107:Acetylation; D042002:Chromatin Assembly and Disassembly; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C494041:ETS1 protein, human; C546783:MIRN192 microRNA, human; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt