Sirtuin E is a fungal global transcriptional regulator that determines the transition from the primary growth to the stationary phase
Sirtuin E is a fungal global transcriptional regulator that determines the transition from the primary growth to the stationary phase
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DOI：
10.1074/jbc.m116.753772
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Eriko Itoh;Rika Odakura;Ken-Ichi Oinuma;Motoyuki Shimizu;Shunsuke Masuo;N. Takaya
中科院分区：
文献类型：
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作者：
Eriko Itoh;Rika Odakura;Ken-Ichi Oinuma;Motoyuki Shimizu;Shunsuke Masuo;N. Takaya
为了响应有限的营养，真菌细胞退出初级生长期，进入稳定期，并停止增殖。虽然在许多环境中对微生物生理学至关重要，但对这种转变的调节知之甚少，但可能涉及许多转录调节因子。这些可能包括sirtuins，其使组蛋白的乙酰赖氨酸残基脱乙酰化并表观遗传地调节整体转录。因此，我们研究的作用，核sirtuin，sirtuin E（SirE），从子囊菌真菌构巢曲霉。了全境当野生型中sirE表达水平增加时，具有破坏的sirE基因（SirEΔ）的构巢菌菌株在稳定生长期积累更多的乙酰化组蛋白H3。SirEΔ抑制了菌丝体的自溶、分生孢子的发育、杂色曲霉素的合成和胞外水解酶的产生。此外，参与这些过程的基因的转录也减少了，表明SirE是一种组蛋白脱乙酰酶，在静止生长期上调这些活性。转录组分析表明，SirE抑制初级碳和氮代谢和细胞壁的合成。染色质免疫沉淀表明，SirE在α-1，3-葡聚糖合酶（agsB）、糖酵解磷酸果糖激酶（pfkA）和甘油醛3-磷酸（gpdA）基因启动子处使组蛋白H3中的乙酰化赖氨酸-9残基脱乙酰，表明SirE抑制这些主要代谢基因的表达。总之，这些结果表明，SirE促进从初级生长期到稳定期的代谢过渡。由于在稳定期观察到的基因表达谱与碳饥饿引起的基因表达谱相匹配，因此SirE似乎通过与饥饿反应相关的机制来控制这种代谢转变。
In response to limited nutrients, fungal cells exit the primary growth phase, enter the stationary phase, and cease proliferation. Although fundamental to microbial physiology in many environments, the regulation of this transition is poorly understood but likely involves many transcriptional regulators. These may include the sirtuins, which deacetylate acetyllysine residues of histones and epigenetically regulate global transcription. Therefore, we investigated the role of a nuclear sirtuin, sirtuin E (SirE), from the ascomycete fungus Aspergillus nidulans. An A. nidulans strain with a disrupted sirE gene (SirEΔ) accumulated more acetylated histone H3 during the stationary growth phase when sirE was expressed at increased levels in the wild type. SirEΔ exhibited decreased mycelial autolysis, conidiophore development, sterigmatocystin biosynthesis, and production of extracellular hydrolases. Moreover, the transcription of the genes involved in these processes was also decreased, indicating that SirE is a histone deacetylase that up-regulates these activities in the stationary growth phase. Transcriptome analyses indicated that SirE repressed primary carbon and nitrogen metabolism and cell-wall synthesis. Chromatin immunoprecipitation demonstrated that SirE deacetylates acetylated Lys-9 residues in histone H3 at the gene promoters of α-1,3-glucan synthase (agsB), glycolytic phosphofructokinase (pfkA), and glyceraldehyde 3-phosphate (gpdA), indicating that SirE represses the expression of these primary metabolic genes. In summary, these results indicate that SirE facilitates the metabolic transition from the primary growth phase to the stationary phase. Because the observed gene expression profiles in stationary phase matched those resulting from carbon starvation, SirE appears to control this metabolic transition via a mechanism associated with the starvation response.