Rpd3p relocation mediates a transcriptional response to rapamycin in yeast
Rpd3p relocation mediates a transcriptional response to rapamycin in yeast
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DOI：
10.1016/j.chembiol.2004.03.001
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发表时间：
2004-03-01
影响因子：
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通讯作者：
Schreiber, SL
中科院分区：
文献类型：
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作者：
Humphrey, EL;Shamji, AF;Schreiber, SL
用雷帕霉素（一种抑制 TOR 蛋白的小分子）处理酵母细胞会导致许多基因受到抑制 [1, 2]。与之前的研究一致，我们发现编码组蛋白脱乙酰酶 (HDAC) 的 RPD3 是雷帕霉素治疗抑制所必需的。为了阐明 RPD3 介导的抑制机制，我们在雷帕霉素处理前后筛选了酵母中 Rpd3p 占据的所有启动子。我们发现 Rpd3p 仅在治疗后才与雷帕霉素抑制基因的启动子结合。这些数据与先前提出的模型相冲突，该模型表明 Rpd3p 与雷帕霉素抑制基因组成型结合，并且仅在雷帕霉素治疗等刺激后才变得活跃 [3-5]。相反，这里提出的综合分析强烈支持这样一种模型，其中将 Rpd3p 招募到基因启动子是控制基因抑制的一个调节步骤 [6]。
Treating yeast cells with rapamycin, a small molecule that inhibits the TOR proteins, leads to the repression of many genes [1, 2]. Consistent with prior studies, we find that RPD3, which encodes a histone deacetylase (HDAC), is required for repression upon rapamycin treatment. To elucidate the mechanism underlying RPD3-mediated repression, we screened all promoters in yeast for occupancy by Rpd3p before and after treatment with rapamycin. We find that Rpd3p binds to the promoters of rapamycin-repressible genes only following treatment. These data conflict with a previously proposed model suggesting that Rpd3p is constitutively bound to rapamycin-repressible genes and becomes active only after a stimulus such as treatment with rapamycin [3-5]. Rather, the comprehensive analysis presented here strongly supports a model in which recruitment of Rpd3p to gene promoters is a regulated step in the control of gene repression [6].