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

Autor: Keightley MC; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia., Carradice DP; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia., Layton JE; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.; Ludwig Institute for Cancer Research, Melbourne-Parkville Branch, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia., Pase L; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia., Bertrand JY; Department of Pathology and Immunology, University of Geneva-CMU, 1211 Geneva 4, Switzerland., Wittig JG; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia., Dakic A; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia., Badrock AP; Faculty of Life Sciences, The University of Manchester, Manchester M13 9PL, UK., Cole NJ; Motor Neuron Disease Research Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales 2109, Australia., Traver D; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA., Nutt SL; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia., McCoey J; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia., Buckle AM; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia., Heath JK; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.; Ludwig Institute for Cancer Research, Melbourne-Parkville Branch, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia., Lieschke GJ; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.; Ludwig Institute for Cancer Research, Melbourne-Parkville Branch, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2017 Apr 06; Vol. 8, pp. 14911. Date of Electronic Publication: 2017 Apr 06.
DOI: 10.1038/ncomms14911
Abstrakt: 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.
Databáze: MEDLINE
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