Zinc finger protein ZBTB20 promotes Toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription.

TitleZinc finger protein ZBTB20 promotes Toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription.
Publication TypeJournal Article
Year of Publication2013
AuthorsLiu X, Zhang P, Bao Y, Han Y, Wang Y, Zhang Q, Zhan Z, Meng J, Li Y, Li N, Zhang WJ, Cao X
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue27
Pagination11097-102
Date Published2013 Jul 2
Abstract

Toll-like receptor (TLR) signaling is critical in innate response against invading pathogens. However, the molecular mechanisms for full activation of TLR-triggered innate immunity need to be fully elucidated. The broad complex tramtrack bric-a-brac/poxvirus and zinc finger (BTB/POZ) family is a class of transcription factors involved in many biological processes. However, few BTB/POZ proteins were reported to function in innate immune response. Zinc finger and BTB domain-containing 20 (ZBTB20), a member of BTB/POZ family, functions in neurogenesis and represses α-fetoprotein gene transcription in liver. However, the immunological functions of ZBTB20 remain unknown. Here, we found that myeloid cell-specific ZBTB20 KO mice were resistant to endotoxin shock and Escherichia coli-caused sepsis. ZBTB20 deficiency attenuated TLR-triggered production of proinflammatory cytokines and type I IFN in macrophages, which attributed to higher abundance of IκBα protein and impaired activity of NF-κB. Furthermore, ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IκBα gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IκBα gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor IκBα gene transcription.

DOI10.3978/j.issn.2223-4292.2013.06.06
Alternate JournalProc. Natl. Acad. Sci. U.S.A.