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

Keightley, Maria-Cristina
Carradice, Duncan P
Layton, Judith E
Pase, Luke
Wittig, Johannes G
Dakic, Aleksandar
Badrock, Andrew P
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Published in Nature Communications. 2017, vol. 8, p. 14911
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.
PMID: 28382966
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Research group Développement du système hémato-vasculaire chez les vertébrés (920)
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KEIGHTLEY, Maria-Cristina et al. The Pu.1 target gene Zbtb11 regulates neutrophil development through its integrase-like HHCC zinc finger. In: Nature Communications, 2017, vol. 8, p. 14911. https://archive-ouverte.unige.ch/unige:94437

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Deposited on : 2017-05-23

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