Histone acetylation mediates epigenetic regulation of transcriptional reprogramming in insects during metamorphosis, wounding and infection.
Histone acetylation mediates epigenetic regulation of transcriptional reprogramming in insects during metamorphosis, wounding and infection.
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DOI：
10.1186/1742-9994-9-25
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发表时间：
2012-10-04
影响因子：
2.8
通讯作者：
Vilcinskas A
中科院分区：
文献类型：
--
作者：
Mukherjee K;Fischer R;Vilcinskas A
真核生物中的基因表达受组蛋白乙酰化/脱乙酰化调控，组蛋白乙酰化/脱乙酰化是由组蛋白乙酰化转移酶(HATS)和组蛋白脱乙酰基酶(HDACs)介导的表观遗传过程，它们的相对活性受到严格调控。HATS对组蛋白的乙酰化增加了DNA的可及性，促进了基因的表达，而HDAC对乙酰基的去除则具有相反的效果。我们探索了HDACs和HATS在鳞翅目模式寄主Galleria mellonella变态、伤害和感染过程中表观遗传重编程中的作用。我们测量了编码HATS和HDAC组分的基因的表达，以监测每个酶复合体的转录活性，发现这两种酶在化蛹过程中都上调了。特定的HAT抑制剂能够推迟化蛹并降低昆虫在受伤后的存活率，而HDAC抑制剂则加速化蛹和提高存活率。HDAC抑制剂的应用调节了在组织重塑(基质金属蛋白酶)、脓毒症(昆虫金属蛋白酶抑制剂)和宿主防御(抗菌肽)中起关键作用的效应基因的表达，并同时诱导HAT活性，这表明组蛋白乙酰化是由反馈机制调节的。我们还发现昆虫病原真菌金龟子绿僵菌和人类致病菌单核细胞增生性李斯特菌都可以通过扭曲HDAC/HAT平衡来延缓梅隆杆菌的变态。我们的研究提供了第一个证据，证明病原菌可以干扰昆虫体内HDAC和HATS的调节，这些似乎操纵宿主的免疫和发育。我们得出结论，昆虫中的组蛋白乙酰化/去乙酰化在变态和对伤害和感染的反应中介导了转录重编程。
Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) whose opposing activities are tightly regulated. The acetylation of histones by HATs increases DNA accessibility and promotes gene expression, whereas the removal of acetyl groups by HDACs has the opposite effect. We explored the role of HDACs and HATs in epigenetic reprogramming during metamorphosis, wounding and infection in the lepidopteran model host Galleria mellonella. We measured the expression of genes encoding components of HATs and HDACs to monitor the transcriptional activity of each enzyme complex and found that both enzymes were upregulated during pupation. Specific HAT inhibitors were able to postpone pupation and to reduce insect survival following wounding, whereas HDAC inhibitors accelerated pupation and increased survival. The administration of HDAC inhibitors modulated the expression of effector genes with key roles in tissue remodeling (matrix metalloproteinase), the regulation of sepsis (inhibitor of metalloproteinases from insects) and host defense (antimicrobial peptides), and simultaneously induced HAT activity, suggesting that histone acetylation is regulated by a feedback mechanism. We also discovered that both the entomopathogenic fungus Metarhizium anisopliae and the human bacterial pathogen Listeria monocytogenes can delay metamorphosis in G. mellonella by skewing the HDAC/HAT balance. Our study provides for the first evidence that pathogenic bacteria can interfere with the regulation of HDACs and HATs in insects which appear to manipulate host immunity and development. We conclude that histone acetylation/deacetylation in insects mediates transcriptional reprogramming during metamorphosis and in response to wounding and infection.
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影响因子：
3.1
作者：
Altincicek, Boran;Linder, Monica;Vilcinskas, Andreas
通讯作者：
Vilcinskas, Andreas
影响因子：
2.8
作者：
Joyce, Susan A.;Gahan, Cormac G. M.
通讯作者：
Gahan, Cormac G. M.
影响因子：
4
作者：
Midelet-Bourdin, G.;Leleu, G.;Malle, P.
通讯作者：
Malle, P.
影响因子：
4.8
作者：
Pakala, Suresh B.;Bui-Nguyen, Tri M.;Kumar, Rakesh
通讯作者：
Kumar, Rakesh
影响因子：
20.3
作者：
Roger, Thierry;Lugrin, Jerome;Calandra, Thierry
通讯作者：
Calandra, Thierry