PMID:23776228

Citation	Liu, X, Zhang, P, Bao, Y, Han, Y, Wang, Y, Zhang, Q, Zhan, Z, Meng, J, Li, Y, Li, N, Zhang, WJ and Cao, X (2013) Zinc finger protein ZBTB20 promotes toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription. Proc. Natl. Acad. Sci. U.S.A. 110:11097-102
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.
Links	PubMed PMC3704009 Online version:10.1073/pnas.1301257110
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ZBT20		GO:0032728: positive regulation of interferon-beta production	ECO:0000315:		P		Figure 1A the third graph with the knockout of the protein zbt20 shows IFN beta in significantly lowered quanities. This is also shown in figure 3A third graph and figure 3c graph 3 with siRNA interference of ZBT20 resulting in similar effects.	complete CACAO 8626
MOUSE:ZBT20		GO:0032760: positive regulation of tumor necrosis factor production	ECO:0000315:		P		Figure 1A the first graph with the knockout of the protein shows Zbt20 shows that TNF is present in significantly lowered quantities. This is also shown in figure 3A first graph and figure 3c graph 1 with RNA interference of zbt20 production resulting in lowered amount of TNF.	complete CACAO 8627
MOUSE:ZBT20		GO:0032755: positive regulation of interleukin-6 production	ECO:0000315:		P		Figure 1A the third graph with the knockout of the protein Zbt20 shows a lowered amount of interleukin 6 (IL-6) being produced. This is also shown in figure 3A second graph and figure 3c graph 2 with siRNA with zbt20 resulting in lowered quantities of IL-6.	complete CACAO 8631
MOUSE:ZBT20		GO:0032728: positive regulation of interferon-beta production	ECO:0000314:		P		Overexpression of Zbt20 results in figure 3E graph 3, with excess zbt20 expression there is an increased production of interferon beta.	complete CACAO 8634
MOUSE:ZBT20		GO:0032760: positive regulation of tumor necrosis factor production	ECO:0000314:		P		Figure 3E graph 1 demonstrates when zbt20 is overexpressed there is an increased amount of TNF (tumor necrosis factor) produced when compared to the control.	complete CACAO 8636
MOUSE:ZBT20		GO:0032755: positive regulation of interleukin-6 production	ECO:0000314:		P		Figure 3E graph 2 demonstrates that when Zbt20 is overexpressed there is an increased production of interleukin-6 (IL-6) in response when compared to the control.	complete CACAO 8637
MOUSE:ZBT20		GO:0010629: negative regulation of gene expression	ECO:0000315:		P		In fig. 4A and S6 when the control is compared to knockout ZBT20 in immunoblot analysis, the IkB alpha gene shows increased expression of IkBalpha so when Zbt20 is present IkB alph gene transcription is repressed.	complete CACAO 8641
MOUSE:ZBT20		GO:0045892: negative regulation of transcription, DNA-dependent	ECO:0000314:		P		In fig. 6A HEK293 cells were cotransfected with ZBTB20 expressing plasmids while maintaining a constant amount of DNA transfected versus mock normal DNA shows that in this repression fold graph that when the cotransfected plasmid is at its largest the amount of transcription is decreased 10 fold of expression. This amount transcription is decreased is in correlation to the amount of ZBT20 plasmid present.	complete CACAO 8800
MOUSE:ZBT20	involved_in	GO:0032728: positive regulation of interferon-beta production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZBT20	involved_in	GO:0032760: positive regulation of tumor necrosis factor production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZBT20	involved_in	GO:0032755: positive regulation of interleukin-6 production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZBT20	involved_in	GO:0032728: positive regulation of interferon-beta production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZBT20	involved_in	GO:0032760: positive regulation of tumor necrosis factor production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZBT20	involved_in	GO:0032755: positive regulation of interleukin-6 production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZBT20	involved_in	GO:0010629: negative regulation of gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZBT20	involved_in	GO:0045892: negative regulation of transcription, DNA-templated	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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