CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability

EMBO Rep. 2011 Sep 30;12(10):1069-76. doi: 10.1038/embor.2011.151.

Abstract

The nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase SIRT1 is a major metabolic regulator activated by energy stresses such as fasting or calorie restriction. SIRT1 activation during fasting not only relies on the increase in the NAD(+)/NADH ratio caused by energy deprivation but also involves an upregulation of SIRT1 mRNA and protein levels in various metabolic tissues. We demonstrate that SIRT1 expression is controlled systemically by the activation of the cyclic AMP response-element-binding protein upon low nutrient availability. Conversely, in the absence of energetic stress, the carbohydrate response-element-binding protein represses the expression of SIRT1. Altogether, these results demonstrate that SIRT1 expression is tightly controlled at the transcriptional level by nutrient availability and further underscore that SIRT1 is a crucial metabolic checkpoint connecting the energetic status with transcriptional programmes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CHO Cells
  • Cell Line, Tumor
  • Cricetinae
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Fasting
  • Gene Expression Regulation*
  • Hep G2 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / metabolism*
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cyclic AMP Response Element-Binding Protein
  • Mlxipl protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • Sirtuin 1