The Pu.1 target gene Zbtb11 regulates neutrophil development through its integrase-like HHCC zinc finger
- Author(s)
- Keightley, MC; Carradice, DP; Layton, JE; Pase, L; Bertrand, JY; Wittig, JG; Dakic, A; Badrock, AP; Cole, NJ; Traver, D; Nutt, SL; McCoey, J; Buckle, AM; Heath, JK; Lieschke, GJ;
- Journal Title
- Nat Commun
- Publication Type
- Journal Article
- 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.
- Publisher
- Springer Nature
- Research Division(s)
- Molecular Immunology; Development And Cancer
- PubMed ID
- 28382966
- Publisher's Version
- https://doi.org/10.1038/ncomms14911
- Open Access at Publisher's Site
https://www.nature.com/articles/ncomms14911- NHMRC Grants
- NHMRC/280916,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-05-02 03:01:27
Last Modified: 2017-05-03 02:19:13