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

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 rol...

Full description

Bibliographic Details
Main Authors:	Wang, Rui-Hong, Zhao, Tingrui, Cui, Kairong, Hu, Gangqing, Chen, Qiang, Chen, Weiping, Wang, Xin-Wei, Soto-Gutierrez, Alejandro, Zhao, Keji, Deng, Chu-Xia
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922021/

id	pubmed-4922021
recordtype	oai_dc
spelling	pubmed-49220212016-06-28 Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging Wang, Rui-Hong Zhao, Tingrui Cui, Kairong Hu, Gangqing Chen, Qiang Chen, Weiping Wang, Xin-Wei Soto-Gutierrez, Alejandro Zhao, Keji Deng, Chu-Xia Article 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. Nature Publishing Group 2016-06-27 /pmc/articles/PMC4922021/ /pubmed/27346580 http://dx.doi.org/10.1038/srep28633 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Rui-Hong Zhao, Tingrui Cui, Kairong Hu, Gangqing Chen, Qiang Chen, Weiping Wang, Xin-Wei Soto-Gutierrez, Alejandro Zhao, Keji Deng, Chu-Xia
spellingShingle	Wang, Rui-Hong Zhao, Tingrui Cui, Kairong Hu, Gangqing Chen, Qiang Chen, Weiping Wang, Xin-Wei Soto-Gutierrez, Alejandro Zhao, Keji Deng, Chu-Xia Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging
author_facet	Wang, Rui-Hong Zhao, Tingrui Cui, Kairong Hu, Gangqing Chen, Qiang Chen, Weiping Wang, Xin-Wei Soto-Gutierrez, Alejandro Zhao, Keji Deng, Chu-Xia
author_sort	Wang, Rui-Hong
title	Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging
title_short	Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging
title_full	Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging
title_fullStr	Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging
title_full_unstemmed	Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging
title_sort	negative reciprocal regulation between sirt1 and per2 modulates the circadian clock and aging
description	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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922021/
_version_	1613599984986357760

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

Similar Items