We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Pu.1 target gene Zbtb11 regulates neutrophil development through its integrase-like HHCC zinc finger.
- Authors
Keightley, Maria-Cristina; Carradice, Duncan P.; Layton, Judith E.; Pase, Luke; Bertrand, Julien Y.; Wittig, Johannes G.; Dakic, Aleksandar; Badrock, Andrew P.; Cole, Nicholas J.; Traver, David; Nutt, Stephen L.; McCoey, Julia; Buckle, Ashley M.; Heath, Joan K.; Lieschke, Graham J.
- 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.
- Publication
Nature Communications, 2017, Vol 8, Issue 4, p14911
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/ncomms14911