Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles.
Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles.
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DOI：
10.1371/journal.pbio.1001442
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发表时间：
2012
期刊：
影响因子：
9.8
通讯作者：
CycliX Consortium
中科院分区：
文献类型：
--
作者：
Le Martelot G;Canella D;Symul L;Migliavacca E;Gilardi F;Liechti R;Martin O;Harshman K;Delorenzi M;Desvergne B;Herr W;Deplancke B;Schibler U;Rougemont J;Guex N;Hernandez N;Naef F;CycliX Consortium
RNA聚合酶II装载的全基因组节律和动态染色质重塑是小鼠肝脏昼夜周期中周期性基因表达的基础。细胞自主昼夜节律振荡器与昼夜周期的相互作用支配着哺乳动物细胞生理的时间区隔化。为了了解小鼠肝脏全基因组昼夜节律的转录和表观遗传学基础，我们通过RNA聚合酶II （Pol II）生成了时间DNA占用谱，以及组蛋白修饰H3K4me3和H3K36me3的谱。我们使用这些数据来量化不同标记之间的相位和振幅的关系。我们发现启动子上有节奏的Pol II招募，而不是从暂停到生产性延长的有节奏的转变，是昼夜基因转录的基础，这一结论得到了模型的进一步支持。此外，Pol II占用比mRNA积累早3小时，与mRNA的半衰期一致。这两个甲基化标记表明，表观遗传景观是高度动态的，并且在24小时周期内进行了全球重塑。尽管转录基因的启动子在H3K4活性低谷时也有三甲基化，但三甲基化水平平均在Pol II后1小时达到峰值。同时，H3K36三甲基化的节律滞后于转录3小时。最后，Pol II占用和mRNA积累的建模概况确定了三类基因：一类基因在转录和mRNA积累中都表现出节律性，第二类基因具有节律性转录但mRNA水平平坦，第三类基因具有恒定转录但有节律性mRNA。后一类强调小鼠肝脏中广泛存在的时间门控转录后调控。在哺乳动物的器官中，如肝脏，许多代谢和生理过程在24小时周期的特定时间优先发生。这些节律功能的时间取决于内源性生物钟和环境时间线索之间的复杂相互作用，环境时间线索通过视交叉上核的主生物钟或通过进食节奏传递。这些节律可以在几个调节水平上实现，在这里，我们的目标是更好地理解调节昼夜节律的转录和表观遗传变化。我们对RNA聚合酶II （Pol II）和表观遗传组蛋白修饰H3K4me3和H3K36me3在一天中特定时间的位置进行了全基因组分析，并将这些数据与mRNA表达水平联系起来。我们的分析表明，Pol II转录节律在小鼠肝脏中是双相的，在早晨和晚上具有主要的高峰活动。此外，组蛋白标记的动态变化在全基因组范围内滞后转录节奏，表明表观遗传景观可以在24小时周期内重塑。最后，对时间Pol II和mRNA积累谱的定量分析表明，转录后调控显著影响mRNA积累谱的幅度和阶段。虽然许多研究已经分析了转录和染色质状态如何在不可逆的细胞分化过程中被修改，但我们的工作强调了这些状态如何在时间上具有周期性的系统中可逆地进化。
Genome-wide rhythms in RNA polymerase II loading and dynamic chromatin remodeling underlie periodic gene expression during diurnal cycles in the mouse liver. Interactions of cell-autonomous circadian oscillators with diurnal cycles govern the temporal compartmentalization of cell physiology in mammals. To understand the transcriptional and epigenetic basis of diurnal rhythms in mouse liver genome-wide, we generated temporal DNA occupancy profiles by RNA polymerase II (Pol II) as well as profiles of the histone modifications H3K4me3 and H3K36me3. We used these data to quantify the relationships of phases and amplitudes between different marks. We found that rhythmic Pol II recruitment at promoters rather than rhythmic transition from paused to productive elongation underlies diurnal gene transcription, a conclusion further supported by modeling. Moreover, Pol II occupancy preceded mRNA accumulation by 3 hours, consistent with mRNA half-lives. Both methylation marks showed that the epigenetic landscape is highly dynamic and globally remodeled during the 24-hour cycle. While promoters of transcribed genes had tri-methylated H3K4 even at their trough activity times, tri-methylation levels reached their peak, on average, 1 hour after Pol II. Meanwhile, rhythms in tri-methylation of H3K36 lagged transcription by 3 hours. Finally, modeling profiles of Pol II occupancy and mRNA accumulation identified three classes of genes: one showing rhythmicity both in transcriptional and mRNA accumulation, a second class with rhythmic transcription but flat mRNA levels, and a third with constant transcription but rhythmic mRNAs. The latter class emphasizes widespread temporally gated posttranscriptional regulation in the mouse liver. In mammalian organs such as the liver, many metabolic and physiological processes occur preferentially at specific times during the 24-hour daily cycle. The timing of these rhythmic functions depends on a complex interplay between the endogenous circadian clock and environmental timing cues relayed through the master circadian clock in the suprachiasmatic nucleus, or via feeding rhythms. These rhythms can be implemented on several regulatory levels, and here we aimed at a better understanding of the transcriptional and epigenetic changes that regulate diurnal rhythms. We performed genome-wide analysis of the locations of RNA polymerase II (Pol II) and the epigenetic histone modifications H3K4me3 and H3K36me3 at specific times of day, relating these data to mRNA expression levels. Our analyses show that Pol II transcriptional rhythms are biphasic in mouse liver, having predominant peak activities in the morning and evening. Moreover, dynamic changes in histone marks lag transcription rhythms genome-wide, indicating that the epigenetic landscape can be remodeled during the 24-hour cycle. Finally, a quantitative analysis of temporal Pol II and mRNA accumulation profiles indicates that posttranscriptional regulation significantly contributes to the amplitude and phase of mRNA accumulation profiles. While many studies have analyzed how transcription and chromatin states are modified during irreversible cell differentiation processes, our work highlights how these states can evolve reversibly in a system exhibiting periodicity in time.
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影响因子：
16.8
作者：
de Almeida, Sergio Fernandes;Grosso, Ana Rita;Carmo-Fonseca, Maria
通讯作者：
Carmo-Fonseca, Maria
DOI：
10.1126/science.1198125
发表时间：
2011-03-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Feng D;Liu T;Sun Z;Bugge A;Mullican SE;Alenghat T;Liu XS;Lazar MA
通讯作者：
Lazar MA
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
昼夜节律的代谢和能量学的融合。
DOI：
10.1126/science.1195027
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bass J;Takahashi JS
通讯作者：
Takahashi JS
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y