In eukaryotes, single cells in a population display different transcriptional profiles. One of the factors regulating this heterogeneity is the chromatin state in each cell. However, the mechanisms of epigenetic chromatin regulation of specific chromosomal regions remain unclear. Therefore, we used single-cell tracking system to analyze IMD2. IMD2 is located at the subtelomeric region of budding yeast, and its expression is epigenetically regulated by heterochromatin fluctuations. Treatment with mycophenolic acid, an inhibitor of de novo GTP biosynthesis, triggered a decrease in GTP, which caused heterochromatin fluctuations at the IMD2 locus. Interestingly, within individually tracked cells, IMD2 expression state underwent repeated switches even though IMD2 is positioned within the heterochromatin region. We also found that 30% of the cells in a population always expressed IMD2. Furthermore, the addition of nicotinamide, a histone deacetylase inhibitor, or guanine, the GTP biosynthesis factor in salvage pathway of GTP biosynthesis, regulated heterogeneity, resulting in IMD2 expression being uniformly induced or suppressed in the population. These results suggest that gene expression heterogeneity in the IMD2 region is regulated by changes in chromatin structure triggered by slight decreases in GTP.

中文翻译：

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酿酒酵母亚端粒区域异染色质波动的 GTP 依赖性调节

在真核生物中，群体中的单个细胞表现出不同的转录谱。调节这种异质性的因素之一是每个细胞中的染色质状态。然而，特定染色体区域的表观遗传染色质调控机制仍不清楚。因此，我们使用单细胞跟踪系统来分析IMD2。IMD2位于芽殖酵母的亚端粒区域，其表达受到异染色质波动的表观遗传调控。用霉酚酸（一种 GTP 从头生物合成抑制剂）治疗会引发 GTP 减少，从而导致IMD2基因座异染色质波动。有趣的是，在单独跟踪的细胞内，即使IMD2位于异染色质区域内，IMD2表达状态也会经历重复的转换。我们还发现群体中 30% 的细胞始终表达IMD2。此外，添加烟酰胺（一种组蛋白脱乙酰酶抑制剂）或鸟嘌呤（GTP生物合成补救途径中的GTP生物合成因子）可调节异质性，导致群体中IMD2表达被均匀诱导或抑制。这些结果表明，IMD2区域的基因表达异质性是由 GTP 轻微降低引发的染色质结构变化调节的。