Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

被引:255
作者
Menet, Jerome S.
Rodriguez, Joseph
Abruzzi, Katharine C.
Rosbash, Michael [1 ]
机构
[1] Brandeis Univ, Howard Hughes Med Inst, Natl Ctr Behav Genom, Waltham, MA 02254 USA
来源
ELIFE | 2012年 / 1卷
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
MESSENGER-RNA STABILITY; LONG NONCODING RNAS; GENE-EXPRESSION; MICROARRAY ANALYSIS; CLOCK; DROSOPHILA; MAMMALS; RHYTHMS; GENOME; ORGANIZATION;
D O I
10.7554/eLife.00011
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
A substantial fraction of the metazoan transcriptome undergoes circadian oscillations in many cells and tissues. Based on the transcription feedback loops important for circadian timekeeping, it is commonly assumed that this mRNA cycling reflects widespread transcriptional regulation. To address this issue, we directly measured the circadian dynamics of mouse liver transcription using Nascent-Seq (genome-wide sequencing of nascent RNA). Although many genes are rhythmically transcribed, many rhythmic mRNAs manifest poor transcriptional rhythms, indicating a prominent contribution of post-transcriptional regulation to circadian mRNA expression. This analysis of rhythmic transcription also showed that the rhythmic DNA binding profile of the transcription factors CLOCK and BMAL1 does not determine the transcriptional phase of most target genes. This likely reflects gene-specific collaborations of CLK: BMAL1 with other transcription factors. These insights from Nascent-Seq indicate that it should have broad applicability to many other gene expression regulatory issues.
引用
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页数:25
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