Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation.
Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation.
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DOI：
10.1016/j.jbc.2021.100533
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
de Bruin RAM
中科院分区：
文献类型：
--
作者：
Cooke SL;Soares BL;Müller CA;Nieduszynski CA;Bastos de Oliveira FM;de Bruin RAM
酿酒酵母呈现基因表达稳态，其定义为在细胞周期的S期，转录水平对DNA拷贝数变化的缓冲作用。有人提出，酿酒酵母利用一种主动机制，通过Rtt109 - Asf1依赖的组蛋白H3在赖氨酸56位（H3K56）的乙酰化来维持基因表达稳态。在此，我们表明基因表达稳态可通过Tos4（Swi6 - 4的靶标）独立于H3K56乙酰化而实现。利用NanoString技术，我们确定Tos4依赖的基因表达稳态取决于其叉头相关（FHA）结构域，这是一个结合组蛋白去乙酰化酶（HDACs）所需的磷酸肽识别结构域。我们证明Tos4依赖的基因表达稳态机制需要其与Rpd3L HDAC复合物相互作用。然而，这与Rpd3在组蛋白去乙酰化以及控制DNA复制时序程序中的既定作用无关，这是通过对荧光激活细胞分选（FACS）的S期和G2期群体进行深度测序所确定的。总体而言，我们的数据显示Tos4通过其FHA结构域依赖的与Rpd3L复合物的相互作用来介导基因表达稳态，而这一过程独立于H3K56ac。
Saccharomyces cerevisiae exhibits gene expression homeostasis, which is defined as the buffering of transcription levels against changes in DNA copy number during the S phase of the cell cycle. It has been suggested that S. cerevisiae employs an active mechanism to maintain gene expression homeostasis through Rtt109-Asf1-dependent acetylation of histone H3 on lysine 56 (H3K56). Here, we show that gene expression homeostasis can be achieved independently of H3K56 acetylation by Tos4 (Target of Swi6-4). Using Nanostring technology, we establish that Tos4-dependent gene expression homeostasis depends on its forkhead-associated (FHA) domain, which is a phosphopeptide recognition domain required to bind histone deacetylases (HDACs). We demonstrate that the mechanism of Tos4-dependent gene expression homeostasis requires its interaction with the Rpd3L HDAC complex. However, this is independent of Rpd3’s well-established roles in both histone deacetylation and controlling the DNA replication timing program, as established by deep sequencing of Fluorescence-Activated Cell Sorted (FACS) S and G2 phase populations. Overall, our data reveals that Tos4 mediates gene expression homeostasis through its FHA domain-dependent interaction with the Rpd3L complex, which is independent of H3K56ac.
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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：
21.3
作者：
Feng, Wenyi;Collingwood, David;Boeck, Max E;Fox, Lindsay A;Alvino, Gina M;Fangman, Walton L;Raghuraman, Mosur K;Brewer, Bonita J
通讯作者：
Brewer, Bonita J
DOI：
10.1083/jcb.201701061
发表时间：
2017-07-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Müller CA;Nieduszynski CA
通讯作者：
Nieduszynski CA
影响因子：
64.5
作者：
Geisberg JV;Moqtaderi Z;Fan X;Ozsolak F;Struhl K
通讯作者：
Struhl K
影响因子：
16
作者：
Kõivomägi M;Valk E;Venta R;Iofik A;Lepiku M;Morgan DO;Loog M
通讯作者：
Loog M