Tissue-specific BMAL1 cistromes reveal that rhythmic transcription is associated with rhythmic enhancer-enhancer interactions
Tissue-specific BMAL1 cistromes reveal that rhythmic transcription is associated with rhythmic enhancer-enhancer interactions
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DOI：
10.1101/gad.322198.118
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发表时间：
2019-03-01
影响因子：
10.5
通讯作者：
Menet, Jerome S.
中科院分区：
文献类型：
--
作者：
Beytebiere, Joshua R.;Trott, Alexandra J.;Menet, Jerome S.
哺乳动物的生物钟依赖于转录因子CLOCK：BMAL 1来协调数千个基因的节律性表达。与生物钟控制下的各种生物功能一致，尽管每个细胞中的时钟机制相同，但节律基因表达是组织特异性的。在这里，我们表明，BMAL 1 DNA结合在很大程度上是组织特异性的，可能是因为组织和组织特异性转录因子的共结合之间的染色质可及性的差异。我们的研究结果还表明，BMAL 1驱动组织特异性节律转录的能力不仅与BMAL 1结合的增强子的活性有关，而且与邻近增强子的活性有关。通过RNA聚合酶II染色质相互作用双末端标签（ChIA-PET）分析BMAL 1增强子与其他顺式调控区之间的物理相互作用的表征揭示了节律性BMAL 1靶基因表达与节律性染色质相互作用相关。因此，这些数据支持BMAL 1靶基因转录的大部分依赖于BMAL 1有节奏地调节增强子网络的能力。
The mammalian circadian clock relies on the transcription factor CLOCK: BMAL1 to coordinate the rhythmic expression of thousands of genes. Consistent with the various biological functions under clock control, rhythmic gene expression is tissue-specific despite an identical clockwork mechanism in every cell. Here we show that BMAL1 DNA binding is largely tissue-specific, likely because of differences in chromatin accessibility between tissues and cobinding of tissue-specific transcription factors. Our results also indicate that BMAL1 ability to drive tissue-specific rhythmic transcription is associated with not only the activity of BMAL1-bound enhancers but also the activity of neighboring enhancers. Characterization of physical interactions between BMAL1 enhancers and other cis-regulatory regions by RNA polymerase II chromatin interaction analysis by paired-end tag (ChIA-PET) reveals that rhythmic BMAL1 target gene expression correlates with rhythmic chromatin interactions. These data thus support that much of BMAL1 target gene transcription depends on BMAL1 capacity to rhythmically regulate a network of enhancers.