scholarly journals Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state

2012 ◽  
Vol 209 (9) ◽  
pp. 1583-1593 ◽  
Author(s):  
Matthew M. Meredith ◽  
Kang Liu ◽  
Alice O. Kamphorst ◽  
Juliana Idoyaga ◽  
Arito Yamane ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Transcription Factor ◽  
Steady State ◽  
Zinc Finger ◽  
Immune Cell ◽  
Negative Regulator ◽  
Binding Motif ◽  
Zinc Finger Transcription Factor ◽  
Mhc Molecules ◽  
Activation Pathways

Classical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. In contrast, during infection or inflammation, cDCs become activated, express higher levels of cell surface MHC molecules, and induce strong adaptive immune responses. We recently identified a cDC-restricted zinc finger transcription factor, zDC (also known as Zbtb46 or Btbd4), that is not expressed by other immune cell populations, including plasmacytoid DCs, monocytes, or macrophages. We define the zDC consensus DNA binding motif and the genes regulated by zDC using chromatin immunoprecipitation and deep sequencing. By deleting zDC from the mouse genome, we show that zDC is primarily a negative regulator of cDC gene expression. zDC deficiency alters the cDC subset composition in the spleen in favor of CD8+ DCs, up-regulates activation pathways in steady-state cDCs, including elevated MHC II expression, and enhances cDC production of vascular endothelial growth factor leading to increased vascularization of skin-draining lymph nodes. Consistent with these observations, zDC protein expression is rapidly down-regulated after TLR stimulation. Thus, zDC is a TLR-responsive, cDC-specific transcriptional repressor that is in part responsible for preventing cDC maturation in the steady state.

ZAT11, a zinc finger transcription factor, is a negative regulator of nickel ion tolerance in Arabidopsis

2014 ◽  
Vol 33 (12) ◽  
pp. 2015-2021 ◽  
Author(s):  
Xiao-Min Liu ◽  
Jonguk An ◽  
Hay Ju Han ◽  
Sun Ho Kim ◽  
Chae Oh Lim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Negative Regulator ◽  
Nickel Ion ◽  
Zinc Finger Transcription Factor

scholarly journals The Histone Gene Cell Cycle Regulator HiNF-P Is a Unique Zinc Finger Transcription Factor with a Novel Conserved Auxiliary DNA-Binding Motif†

Biochemistry ◽  
2008 ◽  
Vol 47 (44) ◽  
pp. 11415-11423 ◽  
Author(s):  
Ricardo Medina ◽  
Timothy Buck ◽  
Sayyed K. Zaidi ◽  
Angela Miele-Chamberland ◽  
Jane B. Lian ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Dna Binding ◽  
Zinc Finger ◽  
Histone Gene ◽  
Binding Motif ◽  
Zinc Finger Transcription Factor ◽  
Cell Cycle Regulator

scholarly journals Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage

2012 ◽  
Vol 209 (6) ◽  
pp. 1153-1165 ◽  
Author(s):  
Matthew M. Meredith ◽  
Kang Liu ◽  
Guillaume Darrasse-Jeze ◽  
Alice O. Kamphorst ◽  
Heidi A. Schreiber ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transcription Factor ◽  
Zinc Finger ◽  
Immune Cell ◽  
Cell Lineage ◽  
Cell Populations ◽  
Zinc Finger Transcription Factor ◽  
Bone Marrow Precursor ◽  
Plasmacytoid Dcs ◽  
Bone Marrow Chimeras

Classical dendritic cells (cDCs), monocytes, and plasmacytoid DCs (pDCs) arise from a common bone marrow precursor (macrophage and DC progenitors [MDPs]) and express many of the same surface markers, including CD11c. We describe a previously uncharacterized zinc finger transcription factor, zDC (Zbtb46, Btbd4), which is specifically expressed by cDCs and committed cDC precursors but not by monocytes, pDCs, or other immune cell populations. We inserted diphtheria toxin (DT) receptor (DTR) cDNA into the 3′ UTR of the zDC locus to serve as an indicator of zDC expression and as a means to specifically deplete cDCs. Mice bearing this knockin express DTR in cDCs but not other immune cell populations, and DT injection into zDC-DTR bone marrow chimeras results in cDC depletion. In contrast to previously characterized CD11c-DTR mice, non-cDCs, including pDCs, monocytes, macrophages, and NK cells, were spared after DT injection in zDC-DTR mice. We compared immune responses to Toxoplasma gondii and MO4 melanoma in DT-treated zDC- and CD11c-DTR mice and found that immunity was only partially impaired in zDC-DTR mice. Our results indicate that CD11c-expressing non-cDCs make significant contributions to initiating immunity to parasites and tumors.

Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli

1999 ◽  
Vol 112 (23) ◽  
pp. 4437-4448 ◽  
Author(s):  
D.M. Stone ◽  
M. Murone ◽  
S. Luoh ◽  
W. Ye ◽  
M.P. Armanini ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Amino Acid ◽  
Zinc Finger ◽  
Hedgehog Signaling ◽  
Adaptor Protein ◽  
Negative Regulator ◽  
Calculated Molecular Mass ◽  
Zinc Finger Transcription Factor ◽  
Suppressor Of Fused ◽  
Sequence Identity

Drosophila Suppressor of fused (Su(fu)) encodes a novel 468-amino-acid cytoplasmic protein which, by genetic analysis, functions as a negative regulator of the Hedgehog segment polarity pathway. Here we describe the primary structure, tissue distribution, biochemical and functional analyses of a human Su(fu) (hSu(fu)). Two alternatively spliced isoforms of hSu(fu) were identified, predicting proteins of 433 and 484 amino acids, with a calculated molecular mass of 48 and 54 kDa, respectively. The two proteins differ only by the inclusion or exclusion of a 52-amino-acid extension at the carboxy terminus. Both isoforms were expressed in multiple embryonic and adult tissues, and exhibited a developmental profile consistent with a role in Hedgehog signaling. The hSu(fu) contains a high-scoring PEST-domain, and exhibits an overall 37% sequence identity (63% similarity) with the Drosophila protein and 97% sequence identity with the mouse Su(fu). The hSu(fu) locus mapped to chromosome 10q24-q25, a region which is deleted in glioblastomas, prostate cancer, malignant melanoma and endometrial cancer. HSu(fu) was found to repress activity of the zinc-finger transcription factor Gli, which mediates Hedgehog signaling in vertebrates, and to physically interact with Gli, Gli2 and Gli3 as well as with Slimb, an F-box containing protein which, in the fly, suppresses the Hedgehog response, in part by stimulating the degradation of the fly Gli homologue. Coexpression of Slimb with Su(fu) potentiated the Su(fu)-mediated repression of Gli. Taken together, our data provide biochemical and functional evidence for the hypothesis that Su(fu) is a key negative regulator in the vertebrate Hedgehog signaling pathway. The data further suggest that Su(fu) can act by binding to Gli and inhibiting Gli-mediated transactivation as well as by serving as an adaptor protein, which links Gli to the Slimb-dependent proteasomal degradation pathway.

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