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Interferon regulatory factor 2 binding protein 2b regulates neutrophil versus macrophage fate during zebrafish definitive myelopoiesis.


ABSTRACT: Aproper choice of neutrophil-macrophage progenitor cell fate is essential for the generation of adequate myeloid subpopulations during embryonic development and in adulthood. The network governing neutrophil-macrophage progenitor cell fate has several key determinants, such as myeloid master regulators CCAAT enhancer binding protein alpha (C/EBP?) and spleen focus forming virus proviral integration oncogene (PU.1). Nevertheless, more regulators remain to be identified and characterized. To ensure balanced commitment of neutrophil-macrophage progenitors toward each lineage, the interplay among these determinants is not only synergistic, but also antagonistic. Depletion of interferon regulatory factor 2 binding protein 2b (Irf2bp2b), a well-known negative transcription regulator, results in a bias in neutrophil-macrophage progenitor cell fate in favor of macrophages at the expense of neutrophils during the stage of definitive myelopoiesis in zebrafish embryos. Mechanistic studies indicate that Irf2bp2b acts as a downstream target of C/EBP?, repressing PU.1 expression, and that SUMOylation confers the repressive function of Irf2bp2b. Thus, Irf2bp2b is a novel determinant in the choice of fate of neutrophil-macrophage progenitor cells.

SUBMITTER: Wang L 

PROVIDER: S-EPMC7012491 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Interferon regulatory factor 2 binding protein 2b regulates neutrophil <i>versus</i> macrophage fate during zebrafish definitive myelopoiesis.

Wang Luxiang L   Gao Shuo S   Wang Haihong H   Xue Chang C   Liu Xiaohui X   Yuan Hao H   Wang Zixuan Z   Chen Saijuan S   Chen Zhu Z   de Thé Hugues H   Zhang Yiyue Y   Zhang Wenqing W   Zhu Jun J   Zhou Jun J  

Haematologica 20200131 2


Aproper choice of neutrophil-macrophage progenitor cell fate is essential for the generation of adequate myeloid subpopulations during embryonic development and in adulthood. The network governing neutrophil-macrophage progenitor cell fate has several key determinants, such as myeloid master regulators CCAAT enhancer binding protein alpha (C/EBPα) and spleen focus forming virus proviral integration oncogene (PU.1). Nevertheless, more regulators remain to be identified and characterized. To ensur  ...[more]

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