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.

生物分子凝聚体是自组织的无膜体，参与许多关键的细胞活动，包括核糖体生物合成、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，但其对转录的影响尚不清楚。在这里，我们探讨了脂肪族二醇 1,6-己二醇 (1,6-HD) 对芽殖酵母中 Pol II 转录和核小体占据的影响。正如预期的那样，1,6-HD 是一种能有效破坏生物分子凝聚物的试剂，它强烈抑制热应激诱导的热休克因子 1 调节基因的转录，这些基因此前已被证明会发生物理相互作用并聚结成核内凝聚物。令人惊讶的是，通常用作阴性对照的异构二醇 2,5-HD 在相同条件下消除了热休克因子 1 靶基因的转录。每种试剂还消除了无法检测到合并的基因的转录，包括 Msn2/Msn4 调节的热诱导基因和组成型表达的管家基因。因此，在升高的温度（39°C）下，HDs 有效抑制不同基因的转录，正如染色质免疫沉淀所证明的那样，HDs 通过消除染色质中 RNA 聚合酶的占据来实现这一目的。同时，在所有检查的基因编码和调控区域内，组蛋白 H3 密度至少增加两倍，包括静止常染色位点、沉默异染色位点和 Pol III 转录位点。我们的结果为使用 HD 在研究缩合物在转录控制中的作用提供了警告，并提供了证据表明暴露于这些试剂会引起核小体密度的广泛增加以及伴随的 Pol II 和 Pol III 转录的损失。