Many active genes reproducibly position near nuclear speckles, but the functional significance of this positioning is unknown. Here we show that HSPA1B BAC transgenes and endogenous Hsp70 genes turn on 2–4 min after heat shock (HS), irrespective of their distance to speckles. However, both total HSPA1B mRNA counts and nascent transcript levels measured adjacent to the transgene are approximately twofold higher for speckle-associated alleles 15 min after HS. Nascent transcript level fold-increases for speckle-associated alleles are 12–56-fold and 3–7-fold higher 1–2 h after HS for HSPA1B transgenes and endogenous genes, respectively. Severalfold higher nascent transcript levels for several Hsp70 flanking genes also correlate with speckle association at 37°C. Live-cell imaging reveals that HSPA1B nascent transcript levels increase/decrease with speckle association/disassociation. Initial investigation reveals that increased nascent transcript levels accompanying speckle association correlate with reduced exosome RNA degradation and larger Ser2p CTD-modified RNA polymerase II foci. Our results demonstrate stochastic gene expression dependent on positioning relative to a liquid-droplet nuclear compartment through “gene expression amplification.”

中文翻译：

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通过核斑点关联扩增基因表达

许多活性基因可重复地定位在核斑点附近，但这种定位的功能意义尚不清楚。在这里我们表明HSPA1BBAC 转基因和内源性 Hsp70 基因在热休克 (HS) 后 2-4 分钟开启，无论它们与斑点的距离如何。然而，两者总计HSPA1BHS 后 15 分钟，斑点相关等位基因在转基因附近测得的 mRNA 计数和新生转录物水平大约高出两倍。对于 HSPA1B 转基因和内源基因，HS 后 1-2 小时，斑点相关等位基因的新生转录水平倍数分别增加 12-56 倍和 3-7 倍。几个 Hsp70 侧翼基因的新生转录水平高出数倍也与 37°C 下的斑点关联相关。活细胞成像表明HSPA1B新生转录物水平随着斑点关联/解离而增加/减少。初步研究表明，伴随斑点关联的新生转录物水平增加与外泌体 RNA 降解减少和 Ser2p CTD 修饰的 RNA 聚合酶 II 焦点更大相关。我们的结果表明，随机基因表达依赖于通过“基因表达放大”相对于液滴核室的定位。