Zbtb14 regulates monocyte and macrophage development through inhibiting <i>pu.1</i> expression in zebrafish.

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 <i>zbtb14</i>, a transcription repressor gene belonging to <i>ZBTB</i> family, leads to an aberrant expansion of monocyte/macrophage population in zebrafish. Mechanistically, Zbtb14 functions as a negative regulator of <i>pu.1</i>, 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, <i>ZBTB14</i> is a newly identified gene implicated in both normal and malignant myelopoiesis.