Journal article

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

MC Keightley, DP Carradice, JE Layton, L Pase, JY Bertrand, JG Wittig, A Dakic, AP Badrock, NJ Cole, D Traver, SL Nutt, J McCoey, AM Buckle, JK Heath, GJ Lieschke

Nature Communications | NATURE PUBLISHING GROUP | Published : 2017

Open access

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-coordinatin..

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University of Melbourne Researchers

Grants

Awarded by Australian Research Council


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council (234708 (G.J.L., J.E.L.), 280916 (J.K.H., G.J.L.), 406695 (D.P.C.), 637395 [G.J.L.], 1070687 (G.J.L., M.-C.K.), 461208 (G.J.L.), 1023529 (G.J.L.), 1044754 (G.J.L.), 1022688 (A.M.B.), 1034816 (N.J.C.), 1048278, 1058238 (S.L.N.)), ARC (DP0346823 (G.J.L., J.E.L., J.K.H.)), Cancer Council Victoria (1047660 (G.J.L., M.-C.K.)), National Institutes of Health (R01 HL079545 (G.J.L.)). The Australian Regenerative Medicine Institute is supported by funds from the State Government of Victoria and the Australian Federal Government.