Lessons from Anaplasma phagocytophilum: Chromatin Remodeling by Bacterial Effectors
Kristen E. Rennoll-Bankert and J. Stephen Dumler
Affiliation: Johns Hopkins University School of Medicine, Department of Pathology, 720 Rutland Avenue, Ross 624, Baltimore, Maryland 21205, USA.
Bacterial pathogens can alter global host gene expression via histone modifications and chromatin remodeling
in order to subvert host responses, including those involved with innate immunity, allowing for bacterial survival. Shigella
flexneri, Listeria monocytogenes, Chlamydia trachomatis, and Anaplasma phagocytophilum express effector proteins that
modify host histones and chromatin structure. A. phagocytophilum modulates granulocyte respiratory burst in part by
dampening transcription of several key phagocyte oxidase genes. The A. phagocytophilum protein AnkA localizes to the
myeloid cell nucleus where it binds AT-rich regions in the CYBB promoter and decreases its transcription. AT-rich regions
of DNA are characteristic of matrix attachment regions (MARs) which are critical for chromatin structure and transcription.
MAR-binding proteins, such as SATB1, interact with histone modifying enzymes resulting in altered gene expression.
With A. phagocytophilum infection, histone deacetylase 1 (HDAC1) expression is increased and histone H3 acetylation
is decreased at the CYBB promoter, suggesting a role for AnkA in altering host epigenetics and modulating gene
transcription, at this, and perhaps other loci. This review will focus on how bacterial pathogens alter host epigenetics, by
specifically examining A. phagocytophilum AnkA cis-regulation of CYBB transcription and epigenetic changes associated
Keywords: Anaplasma phagocytophilum, AnkA, CYBB, epigenetics, histone modifications, and NADPH oxidase, Bacterial pathogens, chromatin remodeling, bacterial survival, chromatin structure, matrix attachment regions (MARs), chromatin structure, bacterial pathogens, Intracellular bacterial pathogens, host cells
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