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Zinc finger protein ZBTB20 promotes Toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription.
|Title||Zinc finger protein ZBTB20 promotes Toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Liu X, Zhang P, Bao Y, Han Y, Wang Y, Zhang Q, Zhan Z, Meng J, Li Y, Li N, Zhang WJ, Cao X|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Date Published||2013 Jul 2|
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.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|