Daily transcription cycling in the baboon Much of our knowledge about the important effects of circadian rhythms in physiology comes from studies of mice, which are nocturnal. Mure et al. report transcriptional profiles from many tissues and brain regions in baboons over a 24-hour period (see the Perspective by Millius and Ueda). The results emphasize how extensive rhythmic expression is, with more than 80% of protein-coding genes involved. They also highlight unanticipated differences between the mouse and baboon in the cycling of transcripts in various tissues. The findings provide a comprehensive analysis of circadian variation in gene expression for a diurnal animal closely related to humans. Science, this issue p. eaao0318; see also p. 1210 Daily rhythms of gene expression are analyzed in the baboon. 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 is tissue-specific and confers an additional layer of regulation and identity to the transcriptome of a given tissue. Diurnal gene expression patterns underlie time-of-the-day–specific functional specialization of tissues. However, available circadian gene expression atlases of a few organs are largely from nocturnal vertebrates. We report the diurnal transcriptome of 64 tissues, including 22 brain regions, sampled every 2 hours over 24 hours, from the primate Papio anubis (baboon). Genomic transcription was highly rhythmic, with up to 81.7% of protein-coding genes showing daily rhythms in expression. In addition to tissue-specific gene expression, the rhythmic transcriptome imparts another layer of functional specialization. Most ubiquitously expressed genes that participate in essential cellular functions exhibit rhythmic expression in a tissue-specific manner. The peak phases of rhythmic gene expression clustered around dawn and dusk, with a “quiescent period” during early night. Our findings also unveil a different temporal organization of central and peripheral tissues between diurnal and nocturnal animals.

中文翻译：

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灵长类动物主要神经和外周组织的昼夜转录组图谱

狒狒的日常转录循环我们关于生理节律的重要影响的大部分知识来自对夜间活动的小鼠的研究。穆雷等人。报告了狒狒许多组织和大脑区域在 24 小时内的转录谱（参见 Millius 和 Ueda 的观点）。结果强调了节律性表达的广泛程度，涉及超过 80% 的蛋白质编码基因。他们还强调了小鼠和狒狒在各种组织中转录本循环方面的意外差异。这些发现提供了对与人类密切相关的昼夜动物基因表达昼夜节律变化的综合分析。科学，这个问题 p。eaao0318; 另见第。在狒狒中分析了 1210 种基因表达的日常节律。引言 细胞自主昼夜节律振荡器——活动——休息和进食——禁食的每日循环——之间的相互作用在几乎所有动物组织中产生基因表达的昼夜节律。这些节律控制着不同器官和大脑区域的各种功能的时间，从而提供最佳的健康度。这些节律的慢性破坏容易导致许多疾病和情感障碍，并且是其标志。原理 在啮齿类动物的有限数量组织中进行的时间序列基因表达研究表明，10% 到 40% 的基因组以组织特异性方式表现出约 24 小时的表达节律。然而，来自人类或我们最近的灵长类亲属的不同组织和大脑区域的节律表达数据很少见。这种多组织昼夜基因表达数据对于获得对基因表达的时空协调如何维持正常生理和行为的机制理解是必要的。我们使用 RNA 测序技术来评估狒狒（一种与人类密切相关的灵长类动物）的主要组织和大脑区域中的基因表达，这些狒狒在明确的 24 小时光照-黑暗和进食-禁食时间表下饲养。结果 我们评估了雄性狒狒 64 个不同组织和大脑区域中的基因表达，这些区域在 24 小时内每 2 小时收集一次。狒狒的组织特异性转录组与人类的转录组相当（人类 GTEx 数据集）。我们检测到 > 25,000 个表达的转录本，包括蛋白质编码和非编码 RNA。近 11,000 个基因在所有组织中普遍表达。这些普遍表达的基因 (UEG) 编码基本的细胞功能，例如转录、RNA 加工、DNA 修复、蛋白质稳态和细胞代谢。其余部分在不同的组织组中表达，约 1500 个基因仅在单个组织中表达。在所有组织中都发现了有节奏的转录本，但在给定组织中，循环转录本的数量从 ~200 到 >3000 不等，组织之间的节律转录本库只有有限的重叠。在 11,000 个 UEG 中，绝大多数 (96.6%) 在至少一个组织中显示出 24 小时节律。检测到的 18,000 个蛋白质编码基因中的大多数 (>80%) 也表现出 24 小时的表达节律。跨组织最丰富的节律转录物是核心时钟组件及其直接输出目标。然而，它们的日常节律的相对丰度和稳健性因组织而异。从有机体层面考虑，64 个组织中的全局节律性转录组织成峰值转录的爆发，在清晨和傍晚（当 11,000 个转录物达到其峰值水平时）。相比之下，在傍晚的相对“静止阶段”，恰逢睡眠开始和不进食，只有 700 个有节奏的转录本达到其峰值表达水平。结论 > 80% 的蛋白质编码基因的日常表达节律，编码不同的生化和细胞功能，构成了迄今为止最大的整合细胞类型内和细胞间不同生化功能的调节机制。从转化的角度来看，节律性可能对健康产生重大影响，因为 82。2% 的编码蛋白质的基因被美国食品和药物管理局确定为可药物靶点，显示出转录的周期性变化。灵长类动物的时空基因表达图谱。（左）在 24 小时内对昼行性灵长类动物的 64 个组织进行的基因表达分析表明，82% 的蛋白质编码基因在至少一个组织中具有节律性。（右）节律性表达是组织特异性的，并赋予给定组织的转录组额外的调节和身份层。昼夜基因表达模式是一天中特定时间组织功能特化的基础。然而，一些器官的可用昼夜节律基因表达图谱主要来自夜间脊椎动物。我们报告了 64 个组织的昼夜转录组，包括 22 个大脑区域，在 24 小时内每 2 小时采样一次，来自灵长类 Papio anubis（狒狒）。基因组转录具有高度节律性，高达 81.7% 的蛋白质编码基因在表达中表现出日常节律。除了组织特异性基因表达外，节律性转录组还赋予了另一层功能专业化。大多数参与基本细胞功能的普遍表达的基因以组织特异性方式表现出节律性表达。有节奏的基因表达的高峰期聚集在黎明和黄昏前后，在深夜有一个“静止期”。我们的研究结果还揭示了昼行性动物和夜间活动性动物之间中枢和外周组织的不同时间组织。除了组织特异性基因表达外，节律性转录组还赋予了另一层功能专业化。大多数参与基本细胞功能的普遍表达的基因以组织特异性方式表现出节律性表达。有节奏的基因表达的高峰期聚集在黎明和黄昏前后，在深夜有一个“静止期”。我们的研究结果还揭示了昼行性动物和夜间活动性动物之间中枢和外周组织的不同时间组织。除了组织特异性基因表达外，节律性转录组还赋予了另一层功能专业化。大多数参与基本细胞功能的普遍表达的基因以组织特异性方式表现出节律性表达。有节奏的基因表达的高峰期聚集在黎明和黄昏前后，在深夜有一个“静止期”。我们的研究结果还揭示了昼行性动物和夜间活动性动物之间中枢和外周组织的不同时间组织。在深夜有一个“静止期”。我们的研究结果还揭示了昼行性动物和夜间活动性动物之间中枢和外周组织的不同时间组织。在深夜有一个“静止期”。我们的研究结果还揭示了昼行动物和夜间动物之间中枢和外周组织的不同时间组织。