Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging (microarray expression)

ABSTRACT: Sirtuin 1 (SIRT1) is involved in both aging and circadian-clock regulation, yet the link between the two processes in relation to SIRT1 function is not clear. Using Sirt1-deficient mice, we found that Sirt1 and Period 2 (Per2) constitute a reciprocal negative regulation loop that plays important roles in modulating hepatic circadian rhythmicity and aging. Sirt1-deficient mice exhibited profound premature aging and enhanced acetylation of histone H4 on lysine16 (H4K16) in the promoter of Per2, the latter of which leads to its overexpression; in turn, Per2 suppresses Sirt1 transcription through binding to the Sirt1 promoter at the Clock/Bmal1 site. This negative reciprocal relationship between SIRT1 and PER2 was also observed in human hepatocytes. We further demonstrated that the absence of Sirt1 or the ectopic overexpression of Per2 in the liver resulted in a dysregulated pace of the circadian rhythm. The similar circadian rhythm was also observed in aged wild type mice. The interplay between Sirt1 and Per2 modulates aging gene expression and circadian-clock maintenance. To investigate hepatic SIRT1-dependent aging related genes, livers from wild type mice at 3 months (young), 12 months (middle age), and 19 months (old) of age, as well as Sirt1-deficient mice at 3 months of age were snap frozen and subject to RNA isolation and microarray analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Gangqing Hu

PROVIDER: E-GEOD-54436 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging.

Wang Rui-Hong RH Zhao Tingrui T Cui Kairong K Hu Gangqing G Chen Qiang Q Chen Weiping W Wang Xin-Wei XW Soto-Gutierrez Alejandro A Zhao Keji K Deng Chu-Xia CX

Scientific reports 20160627

Sirtuin 1 (SIRT1) is involved in both aging and circadian-clock regulation, yet the link between the two processes in relation to SIRT1 function is not clear. Using Sirt1-deficient mice, we found that Sirt1 and Period 2 (Per2) constitute a reciprocal negative regulation loop that plays important roles in modulating hepatic circadian rhythmicity and aging. Sirt1-deficient mice exhibited profound premature aging and enhanced acetylation of histone H4 on lysine16 (H4K16) in the promoter of Per2, th ...[more]

PMID: 27346580

Similar Datasets

Project description:Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In fact, Per2-/- mice have larger infarct sizes with a deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we performed lactate measurements during reperfusion in Per1-/-, Per2-/- or wildtype mice followed by gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2-/- mice. Lactate measurements in whole blood confirmed a dominant role of Per2 for lactate production during myocardial ischemia. Surprisingly, high-throughput gene array analysis of eight different conditions on one 24-microarray plate revealed dominantly lipid metabolism as differentially regulated pathway in wildtype mice when compared to Per2-/-. In all treatment groups, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2-/- mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated 'Per2-genes'. Subsequent studies on inflammatory markers showed increasing IL6 or TNFa levels during reperfusion in Per2-/- mice. In summary, these studies reveal a novel role of cardiac Per2 for fatty acid metabolism or inflammation during myocardial ischemia and reperfusion. We pursued studies on Per2 dependent gene expression during myocardial ischemia or reperfusion to understand its impact on cardiac metabolism. We designed different ischemia and reperfusion protocols and performed a high-throughput expression profiling of 24 samples at a time using an industry-standard whole mouse gene array (Affymetrix, Mouse Gene 2.1 ST 24-Array). To understand differential gene regulation during different conditions we performed 1) 30 minutes of ischemia without reperfusion, 2) ischemic preconditioning (IP, 4 x 5 minutes ischemia and reperfusion), as known cardioprotective mechanism, and 3) 30 minutes of ischemia followed by 60 minutes of reperfusion. Based on three arrays per condition the total number of arrays was 24, which we analyzed at the same time on a multi plate array to avoid inter-array variations. Quality analysis using Partek Genomics Suite 6.6 revealed high confidence in the quality of the microarray data and all samples met 'Quality Assurance/Quality Control' (QA/QC) criteria.

Dataset Information

Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging (microarray expression)

Publications

Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure