Zinc finger protein ZBTB20 promotes toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription
Open Access
- 17 June 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (27), 11097-11102
- https://doi.org/10.1073/pnas.1301257110
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.Keywords
This publication has 41 references indexed in Scilit:
- Regulation of Adaptive Immunity by the Innate Immune SystemScience, 2010
- Promyelocytic Leukemia Zinc Finger Protein Regulates Interferon-Mediated Innate ImmunityImmunity, 2009
- Zinc Finger Protein Zbtb20 Is Essential for Postnatal Survival and Glucose HomeostasisMolecular and Cellular Biology, 2009
- Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decayNature, 2009
- Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liverProceedings of the National Academy of Sciences of the United States of America, 2008
- Virus Infection Induces NF-κB-Dependent Interchromosomal Associations Mediating Monoallelic IFN-β Gene ExpressionCell, 2008
- A Novel CCCH-Zinc Finger Protein Family Regulates Proinflammatory Activation of MacrophagesPublished by Elsevier BV ,2008
- Shared Principles in NF-κB SignalingCell, 2008
- The family of five: TIR-domain-containing adaptors in Toll-like receptor signallingNature Reviews Immunology, 2007
- Functional analysis of the role of POK transcriptional repressorsBriefings in Functional Genomics and Proteomics, 2007