2. Academic Validation
  3. Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish

Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish

  • Elife. 2022 Oct 7;11:e80760. doi: 10.7554/eLife.80760.
Yun Deng 1 2,  Haihong Wang 1 2,  Xiaohui Liu 1 2,  Hao Yuan 1 2,  Jin Xu 3,  Hugues de Thé 2 4,  Jun Zhou 1 2,  Jun Zhu 2 4
Affiliations

Affiliations

  • 1 Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 CNRS-LIA Hematology and Cancer, Sino-French Research Center for Life Sciences and Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Laboratory of Immunology and Regeneration, School of Medicine, South China University of Technology, Guangzhou, China.
  • 4 Université de Paris 7/INSERM/CNRS UMR 944/7212, Equipe Labellisée Ligue Nationale Contre le Cancer, Hôpital St. Louis, Paris, France.
PMID: 36205309 DOI: 10.7554/eLife.80760
Abstract

Macrophages and their precursor cells, monocytes, are the first line of defense of the body against foreign pathogens and tissue damage. Although the origins of macrophages are diverse, some common transcription factors (such as PU.1) are required to ensure proper development of monocytes/macrophages. Here, we report that the deficiency of zbtb14, a transcription repressor gene belonging to ZBTB family, leads to an aberrant expansion of monocyte/macrophage population in zebrafish. Mechanistically, Zbtb14 functions as a negative regulator of pu.1, and SUMOylation on a conserved lysine is essential for the repression activity of Zbtb14. Moreover, a serine to phenylalanine mutation found in an acute myeloid leukemia (AML) patient could target ZBTB14 protein to autophagic degradation. Hence, ZBTB14 is a newly identified gene implicated in both normal and malignant myelopoiesis.

Keywords

AML; SUMOylation; Zbtb14; development; developmental biology; macrophage; zebrafish.

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