The histone H3 lysine 56 acetylation pathway is regulated by target of rapamycin (TOR) signaling and functions directly in ribosomal RNA biogenesis.
The histone H3 lysine 56 acetylation pathway is regulated by target of rapamycin (TOR) signaling and functions directly in ribosomal RNA biogenesis.
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DOI：
10.1093/nar/gks345
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发表时间：
2012-08
影响因子：
14.9
通讯作者：
Laribee RN
中科院分区：
文献类型：
--
作者：
Chen H;Fan M;Pfeffer LM;Laribee RN
通过组蛋白翻译后修饰的染色质的表观遗传变化对于改变基因转录以响应环境线索是必不可少的。组蛋白修饰如何受环境刺激的调节仍然知之甚少，但这一过程对于描述表观遗传途径如何受细胞环境的影响至关重要。我们已经使用了雷帕霉素（TOR）通路，它传递环境营养信号来控制细胞生长的目标，作为一个模型来描绘这种现象背后的机制。使用TOR抑制剂雷帕霉素针对组蛋白H3/H4突变体文库的化学基因组学筛选鉴定了组蛋白H3赖氨酸56乙酰化（H3 K56 ac）作为由TOR信号传导调节的染色质修饰。我们证明了这种乙酰化途径在TOR依赖性细胞生长中的作用部分是通过直接促进核糖体RNA（rRNA）的生物合成。具体而言，H3 K56 ac通过调节高迁移率族蛋白Hmo 1和小核糖体亚基（SSU）加工体复合物的结合，创造了允许RNA聚合酶I转录和新生rRNA加工的染色质环境。总的来说，这些研究确定了TOR信号传导的一种新的染色质调节作用，并支持H3 K56 ac在核糖体DNA（rDNA）基因转录和细胞生长所必需的新生rRNA加工中的特异性功能。
Epigenetic changes in chromatin through histone post-translational modifications are essential for altering gene transcription in response to environmental cues. How histone modifications are regulated by environmental stimuli remains poorly understood yet this process is critical for delineating how epigenetic pathways are influenced by the cellular environment. We have used the target of rapamycin (TOR) pathway, which transmits environmental nutrient signals to control cell growth, as a model to delineate mechanisms underlying this phenomenon. A chemical genomics screen using the TOR inhibitor rapamycin against a histone H3/H4 mutant library identified histone H3 lysine 56 acetylation (H3K56ac) as a chromatin modification regulated by TOR signaling. We demonstrate this acetylation pathway functions in TOR-dependent cell growth in part by contributing directly to ribosomal RNA (rRNA) biogenesis. Specifically, H3K56ac creates a chromatin environment permissive to RNA polymerase I transcription and nascent rRNA processing by regulating binding of the high mobility group protein Hmo1 and the small ribosomal subunit (SSU) processome complex. Overall, these studies identify a novel chromatin regulatory role for TOR signaling and support a specific function for H3K56ac in ribosomal DNA (rDNA) gene transcription and nascent rRNA processing essential for cell growth.
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DOI：
10.1126/science.1135862
发表时间：
2007-02-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Driscoll R;Hudson A;Jackson SP
通讯作者：
Jackson SP
影响因子：
64.8
作者：
Cunningham, John T.;Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
--
作者：
Humphrey, EL;Shamji, AF;Schreiber, SL
通讯作者：
Schreiber, SL
影响因子：
16
作者：
Binda, Matteo;Peli-Gulli, Marie-Pierre;De Virgilio, Claudio
通讯作者：
De Virgilio, Claudio
影响因子：
6.8
作者：
Berndsen, Christopher E.;Denu, John M.
通讯作者：
Denu, John M.