Temporal mapping of CEBPA and CEBPB binding during liver regeneration reveals dynamic occupancy and specific regulatory codes for homeostatic and cell cycle gene batteries.
Temporal mapping of CEBPA and CEBPB binding during liver regeneration reveals dynamic occupancy and specific regulatory codes for homeostatic and cell cycle gene batteries.
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DOI：
10.1101/gr.146399.112
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发表时间：
2013-04
期刊：
影响因子：
7
通讯作者：
Porse BT
中科院分区：
文献类型：
--
作者：
Jakobsen JS;Waage J;Rapin N;Bisgaard HC;Larsen FS;Porse BT
转录因子结合的动态变化是通过允许基因转录的快速变化来调节生物过程的核心。然而，很少有全基因组的研究已经检查了如何在高等动物体内的转录因子占用时间协调。在这里，我们量化了两个关键肝细胞转录因子CEBPA和CEBPB（也称为C/EBPalpha和C/EBPbeta）的全基因组结合模式，在小鼠部分肝切除引起的肝再生的高度动态过程中的多个时间点。结合这些配置文件与RNA聚合酶II结合数据，我们发现三个时间类的转录因子结合与不同的调控基因集参与急性期反应，代谢/稳态功能，或细胞周期进程。此外，我们证明了一个以前未被承认的早期阶段的稳态基因表达之前，S期进入。通过分析三类CEBP结合区域，我们发现了相互排斥的序列基序集，表明了CEBP通过与其他因素的差异共结合而募集的时间代码。这些发现通过涉及一组中心转录因子的连续ChIP实验和/或通过与外部ChIP-seq数据进行比较来验证。我们的定量研究不仅提供了参与肝再生的许多新因素的体内证据，而且还指出了调节分化细胞自我更新的电路的相似性。两者合计，我们的工作强调了权力的全球时间分析的转录因子占用阐明机制，调节复杂的高等生物的动态生物过程。
Dynamic shifts in transcription factor binding are central to the regulation of biological processes by allowing rapid changes in gene transcription. However, very few genome-wide studies have examined how transcription factor occupancy is coordinated temporally in vivo in higher animals. Here, we quantified the genome-wide binding patterns of two key hepatocyte transcription factors, CEBPA and CEBPB (also known as C/EBPalpha and C/EBPbeta), at multiple time points during the highly dynamic process of liver regeneration elicited by partial hepatectomy in mouse. Combining these profiles with RNA polymerase II binding data, we find three temporal classes of transcription factor binding to be associated with distinct sets of regulated genes involved in the acute phase response, metabolic/homeostatic functions, or cell cycle progression. Moreover, we demonstrate a previously unrecognized early phase of homeostatic gene expression prior to S-phase entry. By analyzing the three classes of CEBP bound regions, we uncovered mutually exclusive sets of sequence motifs, suggesting temporal codes of CEBP recruitment by differential cobinding with other factors. These findings were validated by sequential ChIP experiments involving a panel of central transcription factors and/or by comparison to external ChIP-seq data. Our quantitative investigation not only provides in vivo evidence for the involvement of many new factors in liver regeneration but also points to similarities in the circuitries regulating self-renewal of differentiated cells. Taken together, our work emphasizes the power of global temporal analyses of transcription factor occupancy to elucidate mechanisms regulating dynamic biological processes in complex higher organisms.
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影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
21.3
作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
DOI：
10.1073/pnas.0711961105
发表时间：
2008-04-22
影响因子：
11.1
作者：
Feng, Ru;Desbordes, Sabrina C.;Graf, Thomas
通讯作者：
Graf, Thomas
影响因子：
29.4
作者：
Laudadio, Ilaria;Manfroid, Isabelle;Lemaigre, Frederic P.
通讯作者：
Lemaigre, Frederic P.
影响因子：
15.9
作者：
GREENBAUM, LE;CRESSMAN, DE;TAUB, R
通讯作者：
TAUB, R