Filtered glucose is mostly reabsorbed by sodium-glucose cotransporter 2 (SGLT2) in the proximal tubules. SGLT2 is predominantly expressed in the human kidney. However, the regulatory mechanisms for gene expression in the human kidney remain unclear. We in this work elucidated the transcriptional regulatory mechanisms for the gene by nucleosome occupancy in the promoter region. Expressions of SGLT2 mRNA and protein were markedly weaker in human kidney-derived HK-2 cells than the human kidney. The nucleosome occupancy level in the promoter region was low in the kidney, but high in HK-2 cells. A treatment with a histone deacetylase inhibitor trichostatin A (TSA) decreased nucleosome occupancy in the promoter region and increased expression levels in HK-2 cells. The upregulation of expression by histone acetylation was accompanied by a higher binding frequency of hepatocyte nuclear factor (HNF) 1, a transcriptional modulator of in the human kidney, to the promoter region. The transfection of a HNF1 expression plasmid into HK-2 cells resulted in the upregulation of SGLT2 mRNA expression in the presence of TSA, but not in the treatment of dimethylsulfoxide as a control. Nucleosome occupancy in the promoter region was markedly higher in the liver and small intestine than the kidney. Our results indicate that tissue-specific nucleosome occupancy plays an important role in the regulation of gene expression via HNF1 binding at the promoter region.
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