Zinc Finger Protein 521 (ZFP521) is required for the development of mast cells in mice (111.16)

Abstract

Abstract Mast cells play crucial roles in both innate and adaptive immune responses. Evidence in our laboratory suggests that the ZFP521 (Evi3/ZNF521/EHZF) transcription factor orchestrates key pathways required for proper development and function of mast cells. ZFP521 is a nuclear protein that contains 30 zinc fingers. ZFP521 is important for the renewal and development of hematopoietic cells. Here, we demonstrate that ZFP521 is expressed highly in murine mast cells. To address the intrinsic roles of ZFP521 in mast cells, we developed a model system in which Zfp521 gene expression is ablated conditionally in mast cells of mice with floxed alleles (Zfp521 cKO mice) by mast cell-specific Cre (Mcpt5-Cre transgene). Zfp521 is required for normal numbers of mast cells in the peritoneal cavity (PMC). In part, the reduction of PMC may be due to the reduced expression of CD117 (c-Kit) on Zfp521 cKO-derived mast cells. Both CD117 and its ligand, Stem Cell Factor (SCF), are essential for mast cell development in the bone marrow. Additionally, the expression of several transcription factors, including GATA-1, GATA-2 and GATA-3, which regulate mast cell development and function is reduced in bone marrow-derived Zfp521 cKO mast cells. Together, our data provide insights into 1) a novel role for ZFP521 in hematopoiesis, and 2) the transcriptional regulatory network that governs the development and function of mast cells.