Chlamydia are Gram-negative, obligate intracellular bacterial pathogens responsible for a broad spectrum of human and animal diseases. In humans, Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection worldwide and is the causative agent of trachoma (infectious blindness) in disadvantaged populations. Over the course of its developmental cycle, Chlamydia extensively remodels its intracellular niche and parasitises the host cell for nutrients, with substantial resulting changes to the host cell transcriptome and proteome. However, little information is available on the impact of chlamydial infection on the host cell epigenome and global gene regulation. Regions of open eukaryotic chromatin correspond to nucleosome-depleted regions, which in turn are associated with regulatory functions and transcription factor binding. We applied formaldehyde-assisted isolation of regulatory elements enrichment followed by sequencing (FAIRE-Seq) to generate temporal chromatin maps of C. trachomatis-infected human epithelial cells in vitro over the chlamydial developmental cycle. We detected both conserved and distinct temporal changes to genome-wide chromatin accessibility associated with C. trachomatis infection. The observed differentially accessible chromatin regions include temporally-enriched sets of transcription factors, which may help shape the host cell response to infection. These regions and motifs were linked to genomic features and genes associated with immune responses, re-direction of host cell nutrients, intracellular signalling, cell–cell adhesion, extracellular matrix, metabolism and apoptosis. This work provides another perspective to the complex response to chlamydial infection, and will inform further studies of transcriptional regulation and the epigenome in Chlamydia-infected human cells and tissues.

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衣原体感染的上皮细胞的染色质可及性动力学

衣原体是革兰氏阴性专性细胞内细菌病原体，可引起广泛的人类和动物疾病。在人类中，沙眼衣原体是全世界最普遍的细菌性传播感染，并且是弱势人群中沙眼的病原体（传染性失明）。在其发展周期的过程中，衣原体广泛地重塑其细胞内生态位，并寄生于宿主细胞中以获取营养，从而导致宿主细胞转录组和蛋白质组发生实质性变化。但是，很少有信息关于衣原体感染对宿主细胞表观基因组和全球基因调控的影响。开放的真核染色质区域对应于核小体耗尽的区域，其又与调节功能和转录因子结合相关。我们应用甲醛辅助分离的调节元素富集，然后测序（FAIRE-Seq）以在衣原体发育周期中体外产生沙眼衣原体感染的人上皮细胞的时间染色质图。我们检测到与沙眼衣原体感染相关的全基因组染色质可及性的保守和独特的时间变化。观察到的差异可访问的染色质区域包括暂时富集的转录因子集，这可能有助于塑造宿主细胞对感染的反应。这些区域和基序与免疫应答，宿主细胞营养的重新定向，细胞内信号传导，细胞间粘附，细胞外基质，代谢和细胞凋亡相关的基因组特征和基因相关。