Phase-separation antagonists potently inhibit transcription and broadly increase nucleosome density.
Phase-separation antagonists potently inhibit transcription and broadly increase nucleosome density.
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相分离拮抗剂有效抑制转录并大致增加核小体密度。
DOI：
10.1016/j.jbc.2022.102365
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发表时间：
2022-10
影响因子：
4.8
通讯作者：
Gross, David S.
中科院分区：
文献类型：
--
作者：
Meduri, Rajyalakshmi;Rubio, Linda S.;Mohajan, Suman;Gross, David S.
生物分子凝聚体是自组织的无膜体，参与许多重要的细胞活动，包括核糖体生物发生、蛋白质合成和基因转录。脂肪醇通常用于研究生物分子缩合物，但它们对转录的影响尚不清楚。在这里，我们探讨了脂肪族二元醇1，6-己二醇(1，6-HD)对芽殖酵母POL II转录和核小体占有率的影响。正如预期的那样，1，6-HD是一种有效地破坏生物分子凝聚体的试剂，它强烈抑制了热应激诱导的热休克因子1调节基因的转录，这些基因以前被证明是物理上相互作用并结合成核内凝聚体的。令人惊讶的是，在相同的条件下，异构体二醇，2，5-HD，通常用作阴性对照，取消了热休克因子1靶基因的转录。每种试剂还取消了未检测到结合的基因的转录，包括MSN2/MSN4调节的热诱导基因和结构性表达的管家基因。因此，在高温(39℃)下，HDs有效地抑制不同基因的转录，染色质免疫沉淀证明了这一点，这是通过取消RNA聚合酶在染色质中的占位来实现的。同时，在所研究的所有基因编码和调控区域中，组蛋白H3的密度至少增加了两倍，包括静止的常染色质基因座、静默的异色色质基因座和PolIII转录的基因座。我们的结果为HDs在研究缩合物在转录控制中的作用提供了一个警告，并提供了证据，即接触这些试剂会引起核小体密度的广泛增加，并伴随着POL II和POL III转录的丢失。
Biomolecular condensates are self-organized membraneless bodies involved in many critical cellular activities, including ribosome biogenesis, protein synthesis, and gene transcription. Aliphatic alcohols are commonly used to study biomolecular condensates, but their effects on transcription are unclear. Here, we explore the impact of the aliphatic dialcohol, 1,6-hexanediol (1,6-HD), on Pol II transcription and nucleosome occupancy in budding yeast. As expected, 1,6-HD, a reagent effective in disrupting biomolecular condensates, strongly suppressed the thermal stress–induced transcription of Heat Shock Factor 1–regulated genes that have previously been shown to physically interact and coalesce into intranuclear condensates. Surprisingly, the isomeric dialcohol, 2,5-HD, typically used as a negative control, abrogated Heat Shock Factor 1–target gene transcription under the same conditions. Each reagent also abolished the transcription of genes that do not detectably coalesce, including Msn2/Msn4-regulated heat-inducible genes and constitutively expressed housekeeping genes. Thus, at elevated temperature (39 °C), HDs potently inhibit the transcription of disparate genes and as demonstrated by chromatin immunoprecipitation do so by abolishing occupancy of RNA polymerase in chromatin. Concurrently, histone H3 density increased at least twofold within all gene coding and regulatory regions examined, including quiescent euchromatic loci, silent heterochromatic loci, and Pol III-transcribed loci. Our results offer a caveat for the use of HDs in studying the role of condensates in transcriptional control and provide evidence that exposure to these reagents elicits a widespread increase in nucleosome density and a concomitant loss of both Pol II and Pol III transcription.
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影响因子：
64.8
作者：
Ahn JH;Davis ES;Daugird TA;Zhao S;Quiroga IY;Uryu H;Li J;Storey AJ;Tsai YH;Keeley DP;Mackintosh SG;Edmondson RD;Byrum SD;Cai L;Tackett AJ;Zheng D;Legant WR;Phanstiel DH;Wang GG
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Milne TA
影响因子：
5.3
作者：
Anandhakumar, Jayamani;Moustafa, Yara W.;Gross, David S.
通讯作者：
Gross, David S.
影响因子：
4
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Höög JL