Transcriptional loops meet chromatin: a dual-layer network controls white-opaque switching in Candida albicans.
Transcriptional loops meet chromatin: a dual-layer network controls white-opaque switching in Candida albicans.
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DOI：
10.1111/j.1365-2958.2009.06772.x
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发表时间：
2009-10
影响因子：
3.6
通讯作者：
Kuchler K
中科院分区：
文献类型：
--
作者：
Hnisz D;Schwarzmüller T;Kuchler K
人类病原体白色念珠菌能够在两种不同的细胞类型（白色和不透明）之间进行可逆转换，这两种细胞类型被认为是具有相同基因组的细胞的不同转录状态。目前的开关调节模型包括由多个转录反馈环控制的主开关基因的双稳态表达。在这里，我们证明染色质修饰酶构成形态发生转换的另一个重要调节层。我们确定八种染色质修饰剂作为开关调节剂。广泛的上位分析将它们映射到至少两个覆盖已知转录网络的独立信号通路。有趣的是，我们将保守的 Set3/Hos2 组蛋白脱乙酰酶复合物确定为关键调节因子，依赖于组蛋白 H3 赖氨酸 4 的甲基化状态进行开关调节。此外，我们证明体外腺嘌呤的存在促进了不透明到白色的转换，但一旦 Set3/Hos2 复合物被破坏，腺嘌呤对转换没有影响。我们的观察假设染色质修饰可能作为通过潜在转录回路整合环境或宿主刺激以确定白色念珠菌细胞命运的一种手段。
The human pathogen Candida albicans is able to undergo a reversible switch between two distinct cell types called white and opaque, which are considered different transcriptional states of cells harbouring identical genomes. The present model of switching regulation includes the bistable expression of a master switch gene that is controlled by multiple transcriptional feedback loops. Here, we show that chromatin-modifying enzymes constitute an additional important regulatory layer of morphogenetic switching. We identify eight chromatin modifiers as switching modulators. Extensive epistasis analysis maps them into at least two independent signalling pathways overlaying the known transcriptional network. Interestingly, we identify the conserved Set3/Hos2 histone deacetylase complex as a key regulator relying on the methylation status of histone H3 lysine 4 for switching modulation. Furthermore, we demonstrate that opaque to white switching is facilitated by the presence of adenine in vitro, but adenine has no effect on switching once the Set3/Hos2 complex is disrupted. Our observations postulate that chromatin modifications may serve as a means to integrate environmental or host stimuli through the underlying transcriptional circuits to determine cell fate in C. albicans.
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影响因子：
56.9
作者：
Domergue, R;Castaño, I;Cormack, BP
通讯作者：
Cormack, BP
DOI：
10.1073/pnas.0605270103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Huang, Guanghua;Wang, Huafeng;Liu, Haoping
通讯作者：
Liu, Haoping
影响因子：
5.3
作者：
MORROW, B;SRIKANTHA, T;SOLL, DR
通讯作者：
SOLL, DR
影响因子：
3.1
作者：
BEDELL, GW;SOLL, DR
通讯作者：
SOLL, DR
影响因子：
--
作者：
Dumitru, Raluca;Navarathna, Dhammika H. M. L. P.;Nickerson, Kenneth W.
通讯作者：
Nickerson, Kenneth W.