Impaired Repopulating Ability of Uhrf2 -/- Hematopoietic Progenitor Cells in Mice.

UHRF proteins catalyze the ubiquitination of target proteins and are involved in regulating gene expression. Some studies reported a reduced expression of UHRF2 in acute leukemia cells, but the role of UHRF2 in hematopoiesis remains unknown. Here, we generated mice to clarify the role of deletion in hematopoiesis. Compared to mice, mice showed no differences in complete blood counts, as well as bone marrow (BM) findings and spleen weights. Proportions of cells in progenitor fractions in BM were comparable between mice and mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of cells were decreased relative to cells in all lineages. After the second BMT, neutrophils were few, while 20-30% of T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in HSPCs in a cleavage under targets and tagmentation assay. While deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that may play a role in the regulation of hematopoiesis.