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FoxO1 deacetylation regulates thyroid hormone-induced transcription of key hepatic gluconeogenic genes.

Publication ,  Journal Article
Singh, BK; Sinha, RA; Zhou, J; Xie, SY; You, S-H; Gauthier, K; Yen, PM
Published in: J Biol Chem
October 18, 2013

Hepatic gluconeogenesis is a concerted process that integrates transcriptional regulation with hormonal signals. A major regulator is thyroid hormone (TH), which acts through its nuclear receptor (TR) to induce the expression of the hepatic gluconeogenic genes, phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC). Forkhead transcription factor FoxO1 also is an important regulator of these genes; however, its functional interactions with TR are not known. Here, we report that TR-mediated transcriptional activation of PCK1 and G6PC in human hepatic cells and mouse liver was FoxO1-dependent and furthermore required FoxO1 deacetylation by the NAD(+)-dependent deacetylase, SirT1. siRNA knockdown of FoxO1 decreased, whereas overexpression of FoxO1 increased, TH-dependent transcriptional activation of PCK1 and G6PC in cultured hepatic cells. FoxO1 siRNA knockdown also decreased TH-mediated transcription in vivo. Additionally, TH was unable to induce FoxO1 deacetylation or hepatic PCK1 gene expression in TH receptor β-null (TRβ(-/-)) mice. Moreover, TH stimulated FoxO1 recruitment to the PCK1 and G6PC gene promoters in a SirT1-dependent manner. In summary, our results show that TH-dependent deacetylation of a second metabolically regulated transcription factor represents a novel mechanism for transcriptional integration of nuclear hormone action with cellular energy status.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

October 18, 2013

Volume

288

Issue

42

Start / End Page

30365 / 30372

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • Thyroid Hormones
  • Sirtuin 1
  • Receptors, Thyroid Hormone
  • Promoter Regions, Genetic
  • Phosphoenolpyruvate Carboxykinase (GTP)
  • Mice, Knockout
  • Mice
  • Male
 

Citation

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Singh, B. K., Sinha, R. A., Zhou, J., Xie, S. Y., You, S.-H., Gauthier, K., & Yen, P. M. (2013). FoxO1 deacetylation regulates thyroid hormone-induced transcription of key hepatic gluconeogenic genes. J Biol Chem, 288(42), 30365–30372. https://doi.org/10.1074/jbc.M113.504845
Singh, Brijesh Kumar, Rohit Anthony Sinha, Jin Zhou, Sherwin Ying Xie, Seo-Hee You, Karine Gauthier, and Paul Michael Yen. “FoxO1 deacetylation regulates thyroid hormone-induced transcription of key hepatic gluconeogenic genes.J Biol Chem 288, no. 42 (October 18, 2013): 30365–72. https://doi.org/10.1074/jbc.M113.504845.
Singh BK, Sinha RA, Zhou J, Xie SY, You S-H, Gauthier K, et al. FoxO1 deacetylation regulates thyroid hormone-induced transcription of key hepatic gluconeogenic genes. J Biol Chem. 2013 Oct 18;288(42):30365–72.
Singh, Brijesh Kumar, et al. “FoxO1 deacetylation regulates thyroid hormone-induced transcription of key hepatic gluconeogenic genes.J Biol Chem, vol. 288, no. 42, Oct. 2013, pp. 30365–72. Pubmed, doi:10.1074/jbc.M113.504845.
Singh BK, Sinha RA, Zhou J, Xie SY, You S-H, Gauthier K, Yen PM. FoxO1 deacetylation regulates thyroid hormone-induced transcription of key hepatic gluconeogenic genes. J Biol Chem. 2013 Oct 18;288(42):30365–30372.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

October 18, 2013

Volume

288

Issue

42

Start / End Page

30365 / 30372

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • Thyroid Hormones
  • Sirtuin 1
  • Receptors, Thyroid Hormone
  • Promoter Regions, Genetic
  • Phosphoenolpyruvate Carboxykinase (GTP)
  • Mice, Knockout
  • Mice
  • Male