%A Li,Zilong %A Lv,Fangqiao %A Dai,Congxin %A Wang,Qiong %A Jiang,Chao %A Fang,Mingming %A Xu,Yong %D 2019 %J Frontiers in Cell and Developmental Biology %C %F %G English %K Transcriptional regulation,epigenetics,liver injury,Hepatocytes,DNA demethylation %Q %R 10.3389/fcell.2019.00310 %W %L %M %P %7 %8 2019-November-26 %9 Original Research %# %! BRG1 regulates LGALS3 transcription %* %< %T Activation of Galectin-3 (LGALS3) Transcription by Injurious Stimuli in the Liver Is Commonly Mediated by BRG1 %U https://www.frontiersin.org/articles/10.3389/fcell.2019.00310 %V 7 %0 JOURNAL ARTICLE %@ 2296-634X %X Galectin-3 (encoded by LGALS3) is a glycan-binding protein that regulates a diverse range of pathophysiological processes contributing to the pathogenesis of human diseases. Previous studies have found that galectin-3 levels are up-regulated in the liver by a host of different injurious stimuli. The underlying epigenetic mechanism, however, is unclear. Here we report that conditional knockout of Brahma related gene (BRG1), a chromatin remodeling protein, in hepatocytes attenuated induction of galectin-3 expression in several different animal models of liver injury. Similarly, BRG1 depletion or pharmaceutical inhibition in cultured hepatocytes suppressed the induction of galectin-3 expression by treatment with LPS plus free fatty acid (palmitate). Further analysis revealed that BRG1 interacted with AP-1 to bind to the proximal galectin-3 promoter and activate transcription. Mechanistically, DNA demethylation surrounding the galectin-3 promoter appeared to be a rate-limiting step in BRG1-mediated activation of galectin-3 transcription. BRG1 recruited the DNA 5-methylcytosine dioxygenase TET1 to the galectin-3 to promote active DNA demethylation thereby activating galectin-3 transcription. Finally, TET1 silencing abrogated induction of galectin-3 expression by LPS plus palmitate in cultured hepatocytes. In conclusion, our data unveil a novel epigenetic pathway that contributes to injury-associated activation of galectin-3 transcription in hepatocytes.