University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Mistimed sleep disrupts circadian regulation of the human transcriptome.

Archer, SN, Laing, EE, Möller-Levet, CS, van der Veen, DR, Bucca, G, Lazar, AS, Santhi, N, Slak, A, Kabiljo, R, von Schantz, M, Smith, CP and Dijk, DJ (2014) Mistimed sleep disrupts circadian regulation of the human transcriptome. Proc Natl Acad Sci U S A.

[img]
Preview
Text
Archer_PNAS_2014.pdf
Available under License : See the attached licence file.

Download (4MB) | Preview
[img]
Preview
Text (licence)
SRI_deposit_agreement.pdf
Available under License : See the attached licence file.

Download (33kB) | Preview

Abstract

Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep-wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep-wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep-wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
AuthorsEmailORCID
Archer, SNUNSPECIFIEDUNSPECIFIED
Laing, EEUNSPECIFIEDUNSPECIFIED
Möller-Levet, CSUNSPECIFIEDUNSPECIFIED
van der Veen, DRUNSPECIFIEDUNSPECIFIED
Bucca, GUNSPECIFIEDUNSPECIFIED
Lazar, ASUNSPECIFIEDUNSPECIFIED
Santhi, NUNSPECIFIEDUNSPECIFIED
Slak, AUNSPECIFIEDUNSPECIFIED
Kabiljo, RUNSPECIFIEDUNSPECIFIED
von Schantz, MUNSPECIFIEDUNSPECIFIED
Smith, CPUNSPECIFIEDUNSPECIFIED
Dijk, DJUNSPECIFIEDUNSPECIFIED
Date : 21 January 2014
Identification Number : 10.1073/pnas.1316335111
Uncontrolled Keywords : biological rhythms, bloodomics, chronobiology, genomics, microarray
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 08 May 2014 10:46
Last Modified : 11 Jun 2014 15:50
URI: http://epubs.surrey.ac.uk/id/eprint/805147

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800