Tup1 is critical for transcriptional repression in Quiescence in S. cerevisiae.

Tup1 is critical for transcriptional repression in Quiescence in S. cerevisiae.
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DOI:
10.1371/journal.pgen.1010559
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发表时间:
2022-12
期刊:
影响因子:
4.5
通讯作者:
--
中科院分区:
生物学2区
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葡萄糖饥饿时,S.酿酒酵母在转录方面显示出显著的改变,导致大规模抑制大多数基因和激活一些其他基因。这与细胞增殖的停滞相一致。这些细胞的一部分进入静止状态,这是一种可逆的非分裂状态。在这里,我们表明,保守的转录辅阻遏Tup 1是至关重要的葡萄糖耗尽后的转录抑制。我们表明,Tup 1-Ssn 6结合新的目标后,葡萄糖耗尽,它仍然作为细胞进入细胞周期的G 0期。此外,我们表明,Tup 1抑制各种葡萄糖代谢和转运基因。我们探索了Tup 1介导的阻遏是如何完成的,并证明了Tup 1与Rpd 3L复合物协调以使H3 K23脱乙酰化。我们发现,Tup 1与Isw 2协调,影响G 0期葡萄糖转运蛋白HXT家族基因的核小体位置。最后,显微镜检查显示,Tup 1缺失的四分之一细胞含有多个DAPI斑点。综上所述,这些发现表明Tup 1在转录重编程中的作用,以响应导致静止状态的环境线索。对于许多生物体的细胞来说,静止是一种非常常见和重要的状态,细胞功能“暂停”,但在适当的条件下可以恢复。大多数微生物以静止状态存在,并在营养物质或其他线索存在时再次开始生长和分裂。在哺乳动物中,静止状态用于维持干细胞群体,癌细胞通常通过进入静止状态来逃避治疗。芽殖酵母酿酒酵母是一个很好的研究静止的模型,因为我们可以很容易地分离出静止的细胞群体。由于芽殖酵母与高等生物共享许多蛋白质和细胞途径,因此我们的研究结果适用于更复杂的系统,这可能与维持健康细胞或提供治疗疾病状态的见解有关。我们知道静止期的一个标志是转录减少,我们对这种变化是如何发生的很感兴趣。我们已经研究了蛋白质Tup 1如何导致细胞静止期基因表达的变化。我们还研究了Tup 1依赖性变化如何依赖于其他染色质相互作用因子,如组蛋白去乙酰化酶Rpd 3,转录因子Xbp 1或染色质重塑蛋白Isw 2。
Upon glucose starvation, S. cerevisiae shows a dramatic alteration in transcription, resulting in wide-scale repression of most genes and activation of some others. This coincides with an arrest of cellular proliferation. A subset of such cells enters quiescence, a reversible non-dividing state. Here, we demonstrate that the conserved transcriptional corepressor Tup1 is critical for transcriptional repression after glucose depletion. We show that Tup1-Ssn6 binds new targets upon glucose depletion, where it remains as the cells enter the G0 phase of the cell cycle. In addition, we show that Tup1 represses a variety of glucose metabolism and transport genes. We explored how Tup1 mediated repression is accomplished and demonstrated that Tup1 coordinates with the Rpd3L complex to deacetylate H3K23. We found that Tup1 coordinates with Isw2 to affect nucleosome positions at glucose transporter HXT family genes during G0. Finally, microscopy revealed that a quarter of cells with a Tup1 deletion contain multiple DAPI puncta. Taken together, these findings demonstrate the role of Tup1 in transcriptional reprogramming in response to environmental cues leading to the quiescent state. Quiescence is a very common and important state for the cells of many organisms, where cell functions ‘pause’ but can resume when the right conditions are met. Most microbes exist in a quiescent state and will start growing and dividing again in the presence of nutrients or other cues. In mammals, a quiescent state is used to maintain stem cell populations and cancer cells often evade treatment by entering quiescence. The budding yeast Saccharomyces cerevisiae is an excellent model for studying quiescence because we can easily isolate populations of quiescent cells. Since budding yeast share many proteins and cellular pathways with higher organisms, our findings are applicable to more complex systems, which may be relevant to maintenance of healthy cells or provide insight to treating disease states. We know that a hallmark of quiescence is reduced transcription, and we are interested in how this change occurs. We have examined how the protein Tup1 causes changes in gene expression in cellular quiescence. We also looked at how Tup1-dependent changes depend on other chromatin interacting factors, such as the histone deacetylase Rpd3, the transcription factor Xbp1, or the chromatin remodeling protein Isw2.
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