The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle.
The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle.
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DOI：
10.1186/s13059-021-02374-3
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发表时间：
2021-06-08
期刊：
影响因子：
12.3
通讯作者：
Fraser P
中科院分区：
文献类型：
--
作者：
Furlan-Magaril M;Ando-Kuri M;Arzate-Mejía RG;Morf J;Cairns J;Román-Figueroa A;Tenorio-Hernández L;Poot-Hernández AC;Andrews S;Várnai C;Virk B;Wingett SW;Fraser P
昼夜节律基因表达对于生物体调节其生理和预测环境中的日常变化至关重要。控制昼夜节律基因转录的分子机制仍在研究中。特别是，在不同的基因组规模和调控元件的染色质构象如何影响节律性基因表达的特点很差。在这里，我们测量在小鼠肝脏中的空间染色质构象的变化，使用全基因组和启动子捕获Hi-C以及基因转录的日常振荡。我们发现拓扑关联域窝藏昼夜节律基因，在一天中的不同时间在转录活性和非活性区室之间切换分配，而它们的边界随着时间的推移稳定地保持它们的结构。为了研究随着时间的推移，在高分辨率的启动子染色质接触，我们应用启动子捕获Hi-C。我们发现，昼夜节律基因启动子显示了最大数量的染色质接触时，他们的峰值转录输出。此外，昼夜节律基因，以及接触和转录的调控元件，在相同的时间点达到最大表达。昼夜节律基因启动子环的锚位点富含肝核受体和其他转录因子的DNA结合位点，一些仅存在于节律或稳定的接触中。最后，通过比较核心时钟和输出昼夜节律基因之间的相互作用概况，我们表明，核心时钟相互作用组比输出昼夜节律基因更动态。我们的研究结果确定了不同尺度的染色质构象动力学，平行振荡基因表达和特征的调控元件，通过节奏或稳定的染色质配置控制昼夜基因转录的剧目。在线版本包含补充材料，可通过10.1186/s13059-021-02374-3获得。
Circadian gene expression is essential for organisms to adjust their physiology and anticipate daily changes in the environment. The molecular mechanisms controlling circadian gene transcription are still under investigation. In particular, how chromatin conformation at different genomic scales and regulatory elements impact rhythmic gene expression has been poorly characterized. Here we measure changes in the spatial chromatin conformation in mouse liver using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription. We find topologically associating domains harboring circadian genes that switch assignments between the transcriptionally active and inactive compartment at different hours of the day, while their boundaries stably maintain their structure over time. To study chromatin contacts of promoters at high resolution over time, we apply promoter capture Hi-C. We find circadian gene promoters displayed a maximal number of chromatin contacts at the time of their peak transcriptional output. Furthermore, circadian genes, as well as contacted and transcribed regulatory elements, reach maximal expression at the same timepoints. Anchor sites of circadian gene promoter loops are enriched in DNA binding sites for liver nuclear receptors and other transcription factors, some exclusively present in either rhythmic or stable contacts. Finally, by comparing the interaction profiles between core clock and output circadian genes, we show that core clock interactomes are more dynamic compared to output circadian genes. Our results identify chromatin conformation dynamics at different scales that parallel oscillatory gene expression and characterize the repertoire of regulatory elements that control circadian gene transcription through rhythmic or stable chromatin configurations. The online version contains supplementary material available at 10.1186/s13059-021-02374-3.
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影响因子：
2.4
作者：
Chen Y;Yamaguchi Y;Suzuki T;Doi M;Okamura H
通讯作者：
Okamura H
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B
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：
4.8
作者：
Chen, F;Ma, L;Shneider, BL
通讯作者：
Shneider, BL
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U