Coordinate genomic association of transcription factors controlled by an imported quorum sensing peptide in Cryptococcus neoformans.
Coordinate genomic association of transcription factors controlled by an imported quorum sensing peptide in Cryptococcus neoformans.
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DOI：
10.1371/journal.pgen.1008744
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发表时间：
2020-09
期刊：
影响因子：
4.5
通讯作者：
Madhani HD
中科院分区：
文献类型：
--
作者：
Summers DK;Perry DS;Rao B;Madhani HD
Qsp1是一种分泌的群体感应肽，是脑膜炎病原菌新型隐球菌毒力所必需的。Qsp1的功能是控制植物生长细胞的细胞壁完整性，也在交配中发挥作用。Qsp 1不是作用于细胞表面受体，而是通过预测的寡肽转运蛋白Opt1导入细胞内发挥作用。在这里，我们确定了一个转录因子网络作为Qsp1的目标。使用全基因组染色质免疫沉淀，我们发现Qsp1控制三个转录因子的基因组关联，其输出由Qsp1调节的基因。这些转录因子之一，Cqs2，也需要在交配过程中的Qsp1的行动，表明它可能是一个共享的Qsp1的近端目标。与这一假设相一致，CQS 2的缺失会影响其他网络转录因子与Qsp 1调控基因的特异性结合。这些遗传学和基因组学研究阐明了输入肽调节真核基因表达的机制。对于许多真菌病原体来说，适应不断变化和多样化环境的能力构成了它们在人体巨噬细胞和其他壁龛内感染和存活的能力的基础。这些变化是由转录因子完成的。许多病原微生物在一个称为群体感应的过程中协调它们的基因表达，作为细胞密度的函数。在这里，在人类真菌脑膜炎病原体新型隐球菌，我们发现，进口真核生物群体感应肽，促进毒力，QSP1，控制三种不同的转录因子的结合启动子，从而调节QSP1调节基因的表达。这一发现揭示了进口肽如何影响基因表达的机制。
Qsp1 is a secreted quorum sensing peptide required for virulence of the fungal meningitis pathogen Cryptococcus neoformans. Qsp1 functions to control cell wall integrity in vegetatively growing cells and also functions in mating. Rather than acting on a cell surface receptor, Qsp1 is imported to act intracellularly via the predicted oligopeptide transporter Opt1. Here, we identify a transcription factor network as a target of Qsp1. Using whole-genome chromatin immunoprecipitation, we find Qsp1 controls the genomic associations of three transcription factors to genes whose outputs are regulated by Qsp1. One of these transcription factors, Cqs2, is also required for the action of Qsp1 during mating, indicating that it might be a shared proximal target of Qsp1. Consistent with this hypothesis, deletion of CQS2 impacts the binding of other network transcription factors specifically to Qsp1-regulated genes. These genetic and genomic studies illuminate mechanisms by which an imported peptide acts to modulate eukaryotic gene expression. For many fungal pathogens, the ability to adapt to changing and diverse environments forms the basis for their ability to infect and survive inside macrophages and other niches in the human body. These changes are accomplished by transcription factors. Many pathogenic microbes coordinate their gene expression as a function of cell density in a process known as quorum sensing. Here, in the human fungal meningitis pathogen Cryptococcus neoformans, we find that an imported eukaryotic quorum sensing peptide that promotes virulence, Qsp1, controls the binding of three different transcription factors to promoters, thereby modulating the expression of Qsp1-regulated genes. This discovery reveals the mechanism for how an imported peptide affects gene expression.
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影响因子：
3.6
作者：
Kozlowicz, Briana K.;Shi, Ke;Dunny, Gary M.
通讯作者：
Dunny, Gary M.
影响因子：
30.3
作者：
Homer CM;Summers DK;Goranov AI;Clarke SC;Wiesner DL;Diedrich JK;Moresco JJ;Toffaletti D;Upadhya R;Caradonna I;Petnic S;Pessino V;Cuomo CA;Lodge JK;Perfect J;Yates JR 3rd;Nielsen K;Craik CS;Madhani HD
通讯作者：
Madhani HD
DOI：
10.1073/pnas.85.12.4369
发表时间：
1988-06-01
影响因子：
11.1
作者：
GROSSMAN, AD;LOSICK, R
通讯作者：
LOSICK, R
影响因子：
5.3
作者：
Kim, TS;Lee, SB;Kang, HS
通讯作者：
Kang, HS
DOI：
10.1073/pnas.1212256110
发表时间：
2013-04-23
影响因子：
11.1
作者：
Chatterjee, Anushree;Cook, Laura C. C.;Hu, Wei-Shou
通讯作者：
Hu, Wei-Shou