Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish
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.
RNA sequencing dataset generated in this study was deposited with Dryad-https://doi.org/10.5061/dryad.9cnp5hqms.
RNA SEQDryad Digital Repository, doi:10.5061/dryad.9cnp5hqms.
Article and author information
National Natural Science Foundation of China (NO.32171097)
- Jun Zhou
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Ethics StatementThe study was approved by the Ethics Committee of Rui Jin Hospital Affiliated toShanghai Jiao Tong University School of Medicine. Zebrafish experimental procedures were conducted in accordance with the protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Shanghai Jiao Tong University (2020-3#).
- Florent Ginhoux, Agency for Science Technology and Research, Singapore
- Received: June 3, 2022
- Preprint posted: July 4, 2022 (view preprint)
- Accepted: October 6, 2022
- Accepted Manuscript published: October 7, 2022 (version 1)
- Version of Record published: October 14, 2022 (version 2)
- Version of Record updated: October 18, 2022 (version 3)
© 2022, Deng et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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