Global Promoter Targeting of a Conserved Lysine Deacetylase for Transcriptional Shutoff during Quiescence Entry
Global Promoter Targeting of a Conserved Lysine Deacetylase for Transcriptional Shutoff during Quiescence Entry
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DOI：
10.1016/j.molcel.2015.07.014
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发表时间：
2015-09-03
期刊：
影响因子：
16
通讯作者：
Tsukiyama, Toshio
中科院分区：
文献类型：
--
作者：
McKnight, Jeffrey N.;Boerma, Joseph W.;Tsukiyama, Toshio
静止是一种保守的细胞周期状态，其特征在于细胞周期停滞、增加的应激抗性、延长的寿命以及降低的转录、翻译和代谢输出。虽然静止在细胞存活和正常分化中起着重要作用，但导致这种状态的分子机制还不清楚。在这里，我们确定了S.酿酒酵母进入静止期。我们的分析揭示了转录关闭比以前认为的要强大得多，以及前所未有的全球染色质转变，这两者密切相关。这些变化需要Rpd3赖氨酸脱乙酰酶通过包括Xbp1和Stb3在内的静止特异性转录因子靶向至少一半的基因启动子。RPD3的缺失阻止细胞建立转录静止，导致静止进入缺陷和时间寿命缩短。我们的研究结果定义了一个高度保守的染色质调节因子驱动的转录组和染色质结构全局重编程的分子机制。
Quiescence is a conserved cell-cycle state characterized by cell-cycle arrest, increased stress resistance, enhanced longevity, and decreased transcriptional, translational, and metabolic output. Although quiescence plays essential roles in cell survival and normal differentiation, the molecular mechanisms leading to this state are not well understood. Here, we determined changes in the transcriptome and chromatin structure of S. cerevisiae upon quiescence entry. Our analyses revealed transcriptional shutoff that is far more robust than previously believed and an unprecedented global chromatin transition, which are tightly correlated. These changes require Rpd3 lysine deacetylase targeting to at least half of gene promoters via quiescence-specific transcription factors including Xbp1 and Stb3. Deletion of RPD3 prevents cells from establishing transcriptional quiescence, leading to defects in quiescence entry and shortening of chronological lifespan. Our results define a molecular mechanism for global reprogramming of transcriptome and chromatin structure for quiescence driven by a highly conserved chromatin regulator.