Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response.
Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response.
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DOI：
10.1016/j.molcel.2022.10.013
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发表时间：
2022-11-17
期刊：
影响因子：
16
通讯作者：
Pincus, David
中科院分区：
文献类型：
--
作者：
Chowdhary, Surabhi;Kainth, Amoldeep S.;Paracha, Sarah;Gross, David S.;Pincus, David
哺乳动物发育和疾病相关基因通过形成称为转录浓缩物的无膜区室来浓缩大量的转录机制。然而，目前尚不清楚这些结构是否在进化上保守或参与3D基因组重组。在这里，我们确定诱导转录缩合物在酵母热休克反应（HSR）。HSR缩合物是序列特异性转录因子热休克因子1（Hsf1）与介体和RNA Pol II的生物药理学动态时空簇。独特的是，HSR凝聚物驱动多个Hsf1靶基因的结合，即使是位于不同染色体上的靶基因。结合的伴侣Hsp70的网站上Hsf1抑制集群，而一个内在的无序区域上Hsf1促进冷凝物的形成和基因间的相互作用。两个Hsf1决定因素的突变重编程HSR凝聚物，成为组成型活性没有基因间的聚结，这是在健身成本。这些结果表明，转录缩合物是真核基因控制的古老而灵活的隔间。Chowdhary等人表明，转录因子Hsf1与Mediator和Pol II一起形成动态转录缩合物，以驱动3D基因组重组，从而在应激期间促进细胞适应性。他们证明转录浓缩物可以存在于哺乳动物谱系之外，并代表真核基因控制的保守元件
Mammalian developmental and disease-associated genes concentrate large quantities of the transcriptional machinery by forming membrane-less compartments known as transcriptional condensates. However, it is unknown whether these structures are evolutionarily conserved or involved in 3D genome reorganization. Here, we identify inducible transcriptional condensates in the yeast heat shock response (HSR). HSR condensates are biophysically dynamic spatiotemporal clusters of the sequence-specific transcription factor Heat shock factor 1 (Hsf1) with Mediator and RNA Pol II. Uniquely, HSR condensates drive the coalescence of multiple Hsf1 target genes, even those located on different chromosomes. Binding of the chaperone Hsp70 to a site on Hsf1 represses clustering, while an intrinsically disordered region on Hsf1 promotes condensate formation and intergenic interactions. Mutation of both Hsf1 determinants reprograms HSR condensates to become constitutively active without intergenic coalescence, which comes at a fitness cost. These results suggest that transcriptional condensates are ancient and flexible compartments of eukaryotic gene control. Chowdhary et al. show that the transcription factor Hsf1, together with Mediator and Pol II, forms dynamic transcriptional condensates to drive 3D genome reorganization that promotes cellular fitness during stress. They demonstrate that transcriptional condensates can exist outside of the mammalian lineage and represent conserved elements of eukaryotic gene control
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影响因子：
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作者：
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通讯作者：
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