Nucleosome positioning and gene regulation of the SGLT2 gene in the renal proximal tubular epithelial cells

Hiroaki Takesue, Takeshi Hirota, Mami Tachimura, Ayane Tokashiki, Ichiro Ieiri

研究成果: ジャーナルへの寄稿学術誌査読

9 被引用数 (Scopus)


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 SGLT2 gene expression in the human kidney remain unclear. We in this work elucidated the transcriptional regulatory mechanisms for the SGLT2 gene by nucleosome occupancy in the SGLT2 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 SGLT2 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 SGLT2 expression levels in HK-2 cells. The upregulation of SGLT2 expression by histone acetylation was accompanied by a higher binding frequency of hepatocyte nuclear factor (HNF) 1a, a transcriptional modulator of SGLT2 in the human kidney, to the promoter region. The transfection of a HNF1a 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 SGLT2 gene expression via HNF1a binding at the SGLT2 promoter region.

ジャーナルMolecular Pharmacology
出版ステータス出版済み - 9月 2018

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 薬理学


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