An injected bacterial effector targets chromatin access for transcription factor NF-κB to alter transcription of host genes involved in immune responses
An injected bacterial effector targets chromatin access for transcription factor NF-κB to alter transcription of host genes involved in immune responses
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DOI：
10.1038/ni1423
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发表时间：
2007-01-01
影响因子：
30.5
通讯作者：
Sansonetti, Philippe J.
中科院分区：
文献类型：
--
作者：
Arbibe, Laurence;Kim, Dong Wook;Sansonetti, Philippe J.
组蛋白H3的丝氨酸10位点磷酸化会增加染色质对参与免疫反应的一部分基因上的转录因子NF - κB的可及性。在此我们报道一种细菌病原体消除了组蛋白H3的磷酸化，以“塑造”受感染宿主细胞的转录反应。我们确定弗氏志贺氏菌的蛋白质效应物OspF是一种双特异性磷酸酶，它使细胞核中的丝裂原活化蛋白激酶去磷酸化，从而以基因特异性的方式阻止组蛋白H3在丝氨酸10位点的磷酸化。OspF的这种活性使志贺氏菌能够阻断一部分NF - κB响应基因的激活，导致多形核白细胞向感染组织的募集受损。因此，弗氏志贺氏菌已经进化出精确调节宿主细胞表观遗传“信息”的能力，以此作为抑制先天免疫的一种策略。
Phosphorylation of histone H3 at Ser10 increases chromatin accessibility to transcription factor NF-kappa B on a subset of genes involved in immune responses. Here we report that a bacterial pathogen abrogated phosphorylation of histone H3 to 'shape' the transcriptional responses of infected host cells. We identify the Shigella flexneri protein effector OspF as a dually specific phosphatase that dephosphorylated mitogen-activated protein kinases in the nucleus, thus preventing histone H3 phosphorylation at Ser10 in a gene-specific way. That activity of OspF enabled shigella to block the activation of a subset of NF-kappa B-responsive genes, leading to compromised recruitment of polymorphonuclear leukocytes to infected tissues. S. flexneri has thus evolved the capacity to precisely modulate host cell epigenetic 'information' as a strategy for repressing innate immunity.