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*
- 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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping