Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans.
Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans.
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DOI：
10.1038/ncomms11704
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发表时间：
2016-05-26
影响因子：
16.6
通讯作者：
Cowen LE
中科院分区：
文献类型：
--
作者：
Leach MD;Farrer RA;Tan K;Miao Z;Walker LA;Cuomo CA;Wheeler RT;Brown AJ;Wong KH;Cowen LE
发烧是对感染的普遍反应，白色念珠菌等机会性病原体已经进化出复杂的电路来感知热度并做出反应。在这里，我们利用 RNA-seq 和 ChIP-seq 发现热休克转录因子 Hsf1 与核小体耗尽的启动子区域中的不同基序结合，以调节热休克基因和参与白色念珠菌毒力的基因。因此，热休克会增加白色念珠菌宿主细胞的粘附、损伤和毒力。 Hsf1 的激活取决于基础和热休克条件下的分子伴侣 Hsp90，但效果是相反的，并且部分受 Hsf1 表达和 DNA 结合水平的控制。最后，我们证明 Hsp90 通过调节应激反应基因启动子的核小体水平来调节全局转录程序。因此，我们描述了白色念珠菌通过 Hsf1 和 Hsp90 对温度做出反应以协调基因表达和染色质结构，从而实现热适应和毒力的机制。 转录因子 Hsf1 和分子伴侣 Hsp90 调节病原体白色念珠菌的热休克反应。在这里，利奇等人。揭示了调节热休克反应和毒力相关基因表达的两个因素之间复杂的相互作用。
Fever is a universal response to infection, and opportunistic pathogens such as Candida albicans have evolved complex circuitry to sense and respond to heat. Here we harness RNA-seq and ChIP-seq to discover that the heat shock transcription factor, Hsf1, binds distinct motifs in nucleosome-depleted promoter regions to regulate heat shock genes and genes involved in virulence in C. albicans. Consequently, heat shock increases C. albicans host cell adhesion, damage and virulence. Hsf1 activation depends upon the molecular chaperone Hsp90 under basal and heat shock conditions, but the effects are opposite and in part controlled at the level of Hsf1 expression and DNA binding. Finally, we demonstrate that Hsp90 regulates global transcription programs by modulating nucleosome levels at promoters of stress-responsive genes. Thus, we describe a mechanism by which C. albicans responds to temperature via Hsf1 and Hsp90 to orchestrate gene expression and chromatin architecture, thereby enabling thermal adaptation and virulence. The transcription factor Hsf1 and the molecular chaperone Hsp90 modulate the heat shock response in the pathogen Candida albicans. Here, Leach et al. reveal a complex interplay between the two factors that regulates the expression of genes involved in the heat shock response and virulence.