BTB-ZF transcriptional regulator PLZF modifies chromatin to restrain inflammatory signaling programs

Anthony John Sadler, Fernando Jaime Rossello, Liang Yu, James Antony Deane, Xiang-Liang Yuan, Die Wang, Aaron Trent Irving, Maria Liaskos, Michael Paul Marie Gantier, Hangjie Ying, Howard Chi Ho Yim, Elizabeth Louise Hartland, Amanda Jill Notini, Carmela Maria De Boer, Stefan White, Ashley Scott Mansell, Jun-Ping Liu, David Neil Watkins, Steven Demetrious Gerondakis, Bryan Raymond George WilliamsDakang Xu

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49 Citations (Scopus)


Inflammation is critical for host defense, but without appropriate control, it can cause chronic disease or even provoke fatal responses. Here we identify a mechanism that limits the inflammatory response. Probing the responses of macrophages to the key sensory Toll-like receptors, we identify that the Broad-complex, Tramtrack and Bric-a-brac/poxvirus and zinc finger (BTB/POZ), transcriptional regulator promyelocytic leukemia zinc finger (PLZF) limits the expression of inflammatory gene products. In accord with this finding, PLZF-deficient animals express higher levels of potent inflammatory cytokines and mount exaggerated inflammatory responses to infectious stimuli. Temporal quantitation of inflammatory gene transcripts shows increased gene induction in the absence of PLZF. Genome-wide analysis of histone modifications distinguish that PLZF establishes basal activity states of early response genes to maintain immune homeostasis and limit damaging inflammation. We show that PLZF stabilizes a corepressor complex that encompasses histone deacetylase activity to control chromatin. Together with our previous demonstration that PLZF promotes the antiviral response, these results suggest a strategy that could realize one of the major goals of immune therapy to retain immune resistance to pathogens while curbing damaging inflammation.
Original languageEnglish
Pages (from-to)1535 - 1540
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
Publication statusPublished - 2015

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