Circadian oscillations of protein-coding and regulatory RNAs in a highly dynamic mammalian liver epigenome.
Circadian oscillations of protein-coding and regulatory RNAs in a highly dynamic mammalian liver epigenome.
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DOI：
10.1016/j.cmet.2012.11.004
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发表时间：
2012-12-05
期刊：
影响因子：
29
通讯作者：
Panda S
中科院分区：
文献类型：
--
作者：
Vollmers C;Schmitz RJ;Nathanson J;Yeo G;Ecker JR;Panda S
在小鼠肝脏中，昼夜节律的转录节律是新陈代谢稳态所必需的。动态的表观基因组修饰是否与转录本的振荡有关还没有系统的研究。我们发现，除了mRNAs，几个反义、Linc和microRNA转录本在成年小鼠肝脏中显示出昼夜节律振荡。强劲的转录振荡通常伴随着启动子、基因体或增强子中具有时间相关性的有节奏的组蛋白修饰，尽管启动子DNA甲基化水平相对稳定。这种整合分析发现，之前未检测到的反义转录本(AsPer2)对编码昼夜节律振荡器组件PER2的基因进行了振荡表达。转录振荡的稳健性经常伴随着多个组蛋白修饰和多个染色质相关时钟成分的重新招募的节律。综上所述，循环组蛋白修饰的位置与其附近的一个或多个振荡转录本的耦合使得能够在哺乳动物肝脏的全基因组、碱基分辨率尺度上建立增强子、基因和转录本之间的时间关系。这些结果为理解代谢、生物钟和染色质修饰之间复杂的动态调节以维持代谢动态平衡提供了一个框架。
In the mouse liver, circadian transcriptional rhythms are necessary for metabolic homeostasis. Whether dynamic epigenomic modifications are associated with transcript oscillations has not been systematically investigated. We found in addition to mRNAs, several antisense-, linc- and micro-RNA transcripts showed circadian oscillations in adult mouse livers. Robust transcript oscillations were often accompanied by temporally correlated rhythmic histone modifications in promoters, gene bodies or enhancers, although promoter DNA methylation levels were relatively stable. Such integrative analyses identified oscillating expression of a previously undetected antisense transcript (asPer2) to the gene encoding the circadian oscillator component Per2. Robustness of transcript oscillations often accompanied rhythms in multiple histone modifications and recruitment of multiple chromatin-associated clock components. In summary, coupling of the locations of cycling histone modifications with one or more oscillating transcripts within their proximity enabled establishment of a temporal relationship between enhancers, genes and transcripts on a genome-wide, base-resolution scale in a mammalian liver. The results offer a framework to understand intricate dynamic regulation among metabolism, circadian clock, and chromatin modifications to maintain metabolic homeostasis.
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影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
29
作者：
Hatori M;Vollmers C;Zarrinpar A;DiTacchio L;Bushong EA;Gill S;Leblanc M;Chaix A;Joens M;Fitzpatrick JA;Ellisman MH;Panda S
通讯作者：
Panda S
DOI：
10.1073/pnas.1118726109
发表时间：
2012-04-03
影响因子：
11.1
作者：
Eckel-Mahan, Kristin L.;Patel, Vishal R.;Sassone-Corsi, Paolo
通讯作者：
Sassone-Corsi, Paolo
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.