Chromatin accessibility dynamics of Chlamydia-infected epithelial cells

Epigenetics & Chromatin

Michael S. Humphrys¹  James W. Marsh²  Wilhelmina M. Huston³  Regan J. Hayward⁴  Garry S. A. Myers⁵ 

[1]Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA

[2]Max Planck Institute for Developmental Biology, Tuebingen, Germany

[3]School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia

[4]The ithree Institute, University of Technology Sydney, Sydney, NSW, Australia

[5]The ithree Institute, University of Technology Sydney, Sydney, NSW, Australia

[6]School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia

关键词: Chlamydial infection;    Chlamydia trachomatis;    Chromatin accessibility;    FAIRE-Seq;    Bacterial infection;   

DOI  :  10.1186/s13072-020-00368-2

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY