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Computational and experimental insights into the circadian effects of SIRT1

The circadian clock orchestrates 24-h rhythms in physiology in most living organisms. At the molecular level, the dogma is that circadian oscillations are based on a negative transcriptional feedback loop. Recent studies found the NAD-dependent histone deacetylase, SIRT1, directly regulates acetylat... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America 06 November 2018, Vol.115(45), pp.11643-11648
Main Author: Foteinou, Panagiota T
Other Authors: Venkataraman, Anand , Francey, Lauren J , Anafi, Ron C , Hogenesch, John B , Doyle, Francis J
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; PMID: 30348778 Version:1 ; DOI: 10.1073/pnas.1803410115
Link: http://pubmed.gov/30348778
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recordid: medline30348778
title: Computational and experimental insights into the circadian effects of SIRT1
format: Article
creator:
  • Foteinou, Panagiota T
  • Venkataraman, Anand
  • Francey, Lauren J
  • Anafi, Ron C
  • Hogenesch, John B
  • Doyle, Francis J
subjects:
  • Sirt1
  • Amplitude
  • Circadian Regulation
  • Computational Model
  • Luminescence Imaging
  • Feedback, Physiological
  • Models, Biological
  • Circadian Clocks -- Genetics
  • Period Circadian Proteins -- Genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha -- Genetics
  • Sirtuin 1 -- Genetics
ispartof: Proceedings of the National Academy of Sciences of the United States of America, 06 November 2018, Vol.115(45), pp.11643-11648
description: The circadian clock orchestrates 24-h rhythms in physiology in most living organisms. At the molecular level, the dogma is that circadian oscillations are based on a negative transcriptional feedback loop. Recent studies found the NAD-dependent histone deacetylase, SIRT1, directly regulates acetylation status of clock components and influences circadian amplitude in cells. While Nakahata et al. [Nakahata Y, Kaluzova M (2008) 134:329-340] reported that loss of increases amplitude through BMAL1 acetylation, Asher et al. [Asher G, Gatfield D (2008) 134:317-328] reported that loss of decreases amplitude through an increase in acetylated PER2. To address this SIRT1 paradox, we developed a circadian enzymatic model. Predictions from this model and experimental validation strongly align with the findings of Asher et al., with PER2 as the primary target of SIRT1. Further, the model suggested SIRT1 influences expression through actions on PGC1α. We validated this finding experimentally. Thus,...
language: eng
source:
identifier: E-ISSN: 1091-6490 ; PMID: 30348778 Version:1 ; DOI: 10.1073/pnas.1803410115
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleComputational and experimental insights into the circadian effects of SIRT1
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subjectSirt1 ; Amplitude ; Circadian Regulation ; Computational Model ; Luminescence Imaging ; Feedback, Physiological ; Models, Biological ; Circadian Clocks -- Genetics ; Period Circadian Proteins -- Genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha -- Genetics ; Sirtuin 1 -- Genetics
descriptionThe circadian clock orchestrates 24-h rhythms in physiology in most living organisms. At the molecular level, the dogma is that circadian oscillations are based on a negative transcriptional feedback loop. Recent studies found the NAD-dependent histone deacetylase, SIRT1, directly regulates acetylation status of clock components and influences circadian amplitude in cells. While Nakahata et al. [Nakahata Y, Kaluzova M (2008) 134:329-340] reported that loss of increases amplitude through BMAL1 acetylation, Asher et al. [Asher G, Gatfield D (2008) 134:317-328] reported that loss of decreases amplitude through an increase in acetylated PER2. To address this SIRT1 paradox, we developed a circadian enzymatic model. Predictions from this model and experimental validation strongly align with the findings of Asher et al., with PER2 as the primary target of SIRT1. Further, the model suggested SIRT1 influences expression through actions on PGC1α. We validated this finding experimentally. Thus,...
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descriptionThe circadian clock orchestrates 24-h rhythms in physiology in most living organisms. At the molecular level, the dogma is that circadian oscillations are based on a negative transcriptional feedback loop. Recent studies found the NAD-dependent histone deacetylase, SIRT1, directly regulates acetylation status of clock components and influences circadian amplitude in cells. While Nakahata et al. [Nakahata Y, Kaluzova M (2008) 134:329-340] reported that loss of increases amplitude through BMAL1 acetylation, Asher et al. [Asher G, Gatfield D (2008) 134:317-328] reported that loss of decreases amplitude through an increase in acetylated PER2. To address this SIRT1 paradox, we developed a circadian enzymatic model. Predictions from this model and experimental validation strongly align with the findings of Asher et al., with PER2 as the primary target of SIRT1. Further, the model suggested SIRT1 influences expression through actions on PGC1α. We validated this finding experimentally. Thus,...
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abstractThe circadian clock orchestrates 24-h rhythms in physiology in most living organisms. At the molecular level, the dogma is that circadian oscillations are based on a negative transcriptional feedback loop. Recent studies found the NAD-dependent histone deacetylase, SIRT1, directly regulates acetylation status of clock components and influences circadian amplitude in cells. While Nakahata et al. [Nakahata Y, Kaluzova M (2008) 134:329-340] reported that loss of increases amplitude through BMAL1 acetylation, Asher et al. [Asher G, Gatfield D (2008) 134:317-328] reported that loss of decreases amplitude through an increase in acetylated PER2. To address this SIRT1 paradox, we developed a circadian enzymatic model. Predictions from this model and experimental validation strongly align with the findings of Asher et al., with PER2 as the primary target of SIRT1. Further, the model suggested SIRT1 influences expression through actions on PGC1α. We validated this finding experimentally. Thus,...
doi10.1073/pnas.1803410115
pmid30348778
date2018-11-06