| First Author | Liu X | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 27 | Pages | 11097-102 |
| PubMed ID | 23776228 | Mgi Jnum | J:219049 |
| Mgi Id | MGI:5619432 | Doi | 10.1073/pnas.1301257110 |
| Citation | Liu X, et al. (2013) Zinc finger protein ZBTB20 promotes Toll-like receptor-triggered innate immune responses by repressing IkappaBalpha gene transcription. Proc Natl Acad Sci U S A 110(27):11097-102 |
| abstractText | 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 alpha-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 IkappaBalpha protein and impaired activity of NF-kappaB. Furthermore, ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IkappaBalpha gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IkappaBalpha gene transcription, govern IkappaBalpha protein expression, and then promote NF-kappaB 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 IkappaBalpha gene transcription. |
