Reversible phase separation of HSF1 is required for an acute transcriptional response during heat shock
Reversible phase separation of HSF1 is required for an acute transcriptional response during heat shock
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热休克期间的急性转录反应需要 HSF1 的可逆相分离
DOI：
10.1038/s41556-022-00846-7
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发表时间：
2022-03
影响因子：
21.3
通讯作者：
Yujie Sun
中科院分区：
文献类型：
--
作者：
Hongchen Zhang;Shipeng Shao;Yong Zeng;Xiaotian Wang;Yizhi Qin;Qiunan Ren;Shengqi Xiang;Yuxin Wang;Junyu Xiao;Yujie Sun
热休克转录因子1（HSF 1）通过增加热休克蛋白的表达来协调对热休克的快速和广泛的细胞反应。然而，HSF 1如何快速和可逆地调节转录重编程仍然不清楚。本文通过结合超分辨率成像、体外重组和高通量测序技术，揭示了HSF 1通过液-液相分离在热休克蛋白基因位点形成小核凝聚物，并通过共相分离富集多个转录器，从而促进靶基因的转录。此外，HSF 1的相分离能力通过调节结构域内特定位点的磷酸化进行微调。最后，我们发现，热休克蛋白70分散HSF 1凝聚物，减弱转录后停止热休克，并进一步阻止凝胶样相变的HSF 1在延长热休克应激。我们的工作揭示了一种可诱导且可逆的相分离反馈机制，用于动态调节HSF 1活性，以驱动转录反应并维持急性应激期间的蛋白质稳态。
Heat-shock transcription factor 1 (HSF1) orchestrates the fast and vast cellular response to heat shock through increased expression of heat-shock proteins. However, how HSF1 rapidly and reversibly regulates transcriptional reprogramming remains poorly defined. Here by combining super-resolution imaging, in vitro reconstitution and high-throughput sequencing, we reveal that HSF1 forms small nuclear condensates via liquid–liquid phase separation at heat-shock-protein gene loci and enriches multiple transcription apparatuses through co-phase separation to promote the transcription of target genes. Furthermore, the phase-separation capability of HSF1 is fine-tuned through phosphorylation at specific sites within the regulatory domain. Last, we discovered that HSP70 disperses HSF1 condensates to attenuate transcription following the cessation of heat shock and further prevents the gel-like phase transition of HSF1 under extended heat-shock stress. Our work reveals an inducible and reversible phase-separation feedback mechanism for dynamic regulation of HSF1 activity to drive the transcriptional response and maintain protein homeostasis during acute stress.
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影响因子：
16.6
作者：
Gomez-Pastor R;Burchfiel ET;Neef DW;Jaeger AM;Cabiscol E;McKinstry SU;Doss A;Aballay A;Lo DC;Akimov SS;Ross CA;Eroglu C;Thiele DJ
通讯作者：
Thiele DJ
影响因子：
5.3
作者：
Kline, MP;Morimoto, RI
通讯作者：
Morimoto, RI
YAP的相位分离重新组织了基因组拓扑，以进行长期YAP靶基因表达。
影响因子：
21.3
作者：
Cai D;Feliciano D;Dong P;Flores E;Gruebele M;Porat-Shliom N;Sukenik S;Liu Z;Lippincott-Schwartz J
通讯作者：
Lippincott-Schwartz J
DOI：
10.1101/283804
发表时间：
2018-03
期刊：
bioRxiv
影响因子：
--
作者：
E. Dine;Agnieszka A Gil;Giselle Uribe;C. Brangwynne;Jared E. Toettcher
通讯作者：
E. Dine;Agnieszka A Gil;Giselle Uribe;C. Brangwynne;Jared E. Toettcher
影响因子：
48
作者：
Levet, Florian;Hosy, Eric;Sibarita, Jean-Baptiste
通讯作者：
Sibarita, Jean-Baptiste