Diurnal transcriptome atlas of a primate across major neural and peripheral tissues

LS Mure, HD Le, G Benegiamo, MW Chang, L Rios… - Science, 2018 - science.org
LS Mure, HD Le, G Benegiamo, MW Chang, L Rios, N Jillani, M Ngotho, T Kariuki…
Science, 2018science.org
INTRODUCTION The interaction among cell-autonomous circadian oscillators—daily cycles
of activity–rest and feeding–fasting—produces diurnal rhythms in gene expression in almost
all animal tissues. These rhythms control the timing of a wide range of functions across
different organs and brain regions, affording optimal fitness. Chronic disruption of these
rhythms predisposes to and are hallmarks of numerous diseases and affective disorders.
RATIONALE Time-series gene expression studies in a limited number of tissues from …
INTRODUCTION
The interaction among cell-autonomous circadian oscillators—daily cycles of activity–rest and feeding–fasting—produces diurnal rhythms in gene expression in almost all animal tissues. These rhythms control the timing of a wide range of functions across different organs and brain regions, affording optimal fitness. Chronic disruption of these rhythms predisposes to and are hallmarks of numerous diseases and affective disorders.
RATIONALE
Time-series gene expression studies in a limited number of tissues from rodents have shown that 10 to 40% of the genome exhibits a ~24-hour rhythm in expression in a tissue-specific manner. However, rhythmic expression data from diverse tissues and brain regions from humans or our closest primate relatives is rare. Such multitissue diurnal gene expression data are necessary for gaining mechanistic understanding of how spatiotemporal orchestration of gene expression maintains normal physiology and behavior. We used a RNA sequencing technique to assess gene expression in major tissues and brain regions from baboons (a primate closely related to humans) housed under a defined 24-hour light–dark and feeding–fasting schedule.
RESULTS
We assessed gene expression in 64 different tissues and brain regions of male baboons, collected every 2 hours over the 24-hour day. Tissue-specific transcriptomes in baboon were comparable with that from humans (Human GTEx data set). We detected >25,000 expressed transcripts, including protein-coding and -noncoding RNAs. Nearly 11,000 genes were commonly expressed in all tissues. These universally expressed genes (UEGs) encoded for basic cellular functions such as transcription, RNA processing, DNA repair, protein homeostasis, and cellular metabolism. The remainders were expressed in distinct sets of tissues, with ~1500 genes expressed exclusively in a single tissue.
Rhythmic transcripts were found in all tissues, but the number of cycling transcripts varied from ~200 to >3000 in a given tissue, with only limited overlap in the repertoire of rhythmic transcripts between tissues. Of the 11,000 UEGs, the vast majority (96.6%) showed 24-hour rhythmicity in at least one tissue. A majority (>80%) of the 18,000 protein-coding genes detected also exhibited 24-hour rhythms in expression. The most enriched rhythmic transcripts across tissues were core clock components and their immediate output targets. However, their relative abundance and robustness of daily rhythms varied across tissues. Considered at the organismal level, global rhythmic transcription in 64 tissues organized into bursts of peak transcription, during early morning and late afternoon (when 11,000 transcripts reach their peak level). By contrast, during a relative “quiescent phase” in early evening that coincides with the onset of sleep and no food intake, only 700 rhythmic transcripts reach their peak expression level.
CONCLUSION
The daily expression rhythms in >80% of protein-coding genes, encoding diverse biochemical and cellular functions, constitutes by far the largest regulatory mechanism that integrates diverse biochemical functions within and across cell types. From a translational point of view, rhythmicity may have a major impact in health because 82.2% of genes coding for proteins that are identified as druggable targets by the U.S. Food and Drug Administration show cyclic changes in transcription.
Spatiotemporal gene expression atlas of a primate
(Left) Gene expression analysis across 64 tissues of a diurnal primate sampled over the 24-hour day shows that 82% of protein-coding genes are rhythmic in at least one tissue. (Right) Rhythmic expression …
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