Transcription organizes euchromatin via microphase separation.

Transcription organizes euchromatin via microphase separation.
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转录通过微相分离组织常染色质。

DOI:
10.1038/s41467-021-21589-3
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发表时间:
2021-03-01
影响因子:
16.6
通讯作者:
Vastenhouw NL
Vastenhouw NL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hilbert L;Sato Y;Kuznetsova K;Bianucci T;Kimura H;Jülicher F;Honigmann A;Zaburdaev V;Vastenhouw NL

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在真核生物中,DNA以染色质的形式包裹在细胞核内,染色质由DNA、蛋白质(如组蛋白)和RNA组成。常染色质是允许转录的,在空间上被组织成转录不活跃的区域,其间散布着转录活性的口袋。虽然转录和RNA与常染色质组织有关,但它们如何相互作用形成和维持转录袋仍不清楚。在这里,我们将理论和实验相结合,分析了多能斑马鱼细胞退出有丝分裂并开始转录时常染色质组织的动力学。我们表明,RNA的积累诱导转录口袋的形成,取代转录无活性的染色质。我们认为,积累的RNA招募了RNA结合蛋白,这些蛋白倾向于从转录不活跃的常染色质中分离出来。由于RNA通过RNA聚合酶与转录的常染色质相连,因此阻止了完全相分离。相反,较小规模的微相出现,不会进一步生长,形成典型的常染色质组织模式。常染色质组织和转录之间的关系尚不清楚。在这里,作者观察到常染色质组织的动力学,表明积累的RNA招募RNA结合蛋白,与转录的常染色质一起从非转录的常染色质分离,形成微相。
In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA. Euchromatin, which is permissive for transcription, is spatially organized into transcriptionally inactive domains interspersed with pockets of transcriptional activity. While transcription and RNA have been implicated in euchromatin organization, it remains unclear how their interplay forms and maintains transcription pockets. Here we combine theory and experiment to analyze the dynamics of euchromatin organization as pluripotent zebrafish cells exit mitosis and begin transcription. We show that accumulation of RNA induces formation of transcription pockets which displace transcriptionally inactive chromatin. We propose that the accumulating RNA recruits RNA-binding proteins that together tend to separate from transcriptionally inactive euchromatin. Full phase separation is prevented because RNA remains tethered to transcribed euchromatin through RNA polymerases. Instead, smaller scale microphases emerge that do not grow further and form the typical pattern of euchromatin organization. How euchromatin organisation and transcription are related is unclear. Here, the authors observe the dynamics of euchromatin organization showing that accumulating RNA recruits RNA-binding proteins that together with transcribed euchromatin separate from non-transcribed euchromatin, forming microphases.
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