PUBLICATION

The Pu.1 target gene Zbtb11 regulates neutrophil development through its integrase-like HHCC zinc finger

Authors
Keightley, M.C., Carradice, D.P., Layton, J.E., Pase, L., Bertrand, J.Y., Wittig, J.G., Dakic, A., Badrock, A.P., Cole, N.J., Traver, D., Nutt, S.L., McCoey, J., Buckle, A.M., Heath, J.K., Lieschke, G.J.
ID
ZDB-PUB-170407-2
Date
2017
Source
Nature communications   8: 14911 (Journal)
Registered Authors
Badrock, Andrew P., Bertrand, Julien, Carradice, Duncan, Cole, Nicholas, Heath, Joan K., Keightley, M. Cristina, Layton, Judy E., Lieschke, Graham J., Pase, Luke, Traver, David, Wittig, Johannes
Keywords
Development, Gene regulation, Myelopoiesis, Transcription factors
Datasets
GEO:GSE94532, GEO:GSE239949
MeSH Terms
  • Zebrafish
  • Databases, Protein
  • Tumor Suppressor Protein p53/metabolism*
  • Zinc Fingers
  • Repressor Proteins/genetics*
  • Animals, Genetically Modified
  • Animals
  • Neutrophils*
  • Proto-Oncogene Proteins/metabolism*
  • Signal Transduction
  • Trans-Activators/metabolism*
  • Zebrafish Proteins/genetics*
  • Leukopoiesis/genetics*
(all 13)
PubMed
28382966 Full text @ Nat. Commun.
Abstract
In response to infection and injury, the neutrophil population rapidly expands and then quickly re-establishes the basal state when inflammation resolves. The exact pathways governing neutrophil/macrophage lineage outputs from a common granulocyte-macrophage progenitor are still not completely understood. From a forward genetic screen in zebrafish, we identify the transcriptional repressor, ZBTB11, as critical for basal and emergency granulopoiesis. ZBTB11 sits in a pathway directly downstream of master myeloid regulators including PU.1, and TP53 is one direct ZBTB11 transcriptional target. TP53 repression is dependent on ZBTB11 cys116, which is a functionally critical, metal ion-coordinating residue within a novel viral integrase-like zinc finger domain. To our knowledge, this is the first description of a function for this domain in a cellular protein. We demonstrate that the PU.1-ZBTB11-TP53 pathway is conserved from fish to mammals. Finally, Zbtb11 mutant rescue experiments point to a ZBTB11-regulated TP53 requirement in development of other organs.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Keightley, M.C., Carradice, D.P., Layton, J.E., Pase, L., Bertrand, J.Y., Wittig, J.G., Dakic, A., Badrock, A.P., Cole, N.J., Traver, D., Nutt, S.L., McCoey, J., Buckle, A.M., Heath, J.K., Lieschke, G.J. (2017) The Pu.1 target gene Zbtb11 regulates neutrophil development through its integrase-like HHCC zinc finger. Nature communications. 8:14911.