Wdr5-mediated H3K4 methylation facilitates HSPC development via maintenance of genomic stability in zebrafish.

ABSTRACT: During fetal stage, hematopoietic stem and progenitor cells (HSPCs) undergo rapid proliferation with a tight control of genomic stability. Although histone H3 lysine 4 (H3K4) methylation has been reported to stabilize the genome in proliferating cells, its specific role in HSPC development remains elusive. In this study, we demonstrated that tryptophan-aspartic acid (WD) repeat protein 5 (Wdr5)-mediated H3K4 methylation is crucial for maintaining genomic stability of proliferating HSPCs in zebrafish embryos. Loss of wdr5 led to a severe reduction of HSPC pool in the caudal hematopoietic tissue, accompanied with attenuated H3K4 methylation level and evident p53-dependent apoptosis in the HSPCs. Mechanistically, Wdr5-mediated H3K4 methylation maintains genomic stability by inhi

SUBMITTER: Wang X 

PROVIDER: S-EPMC11962412 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature