TiF1-gamma plays an essential role in murine hematopoiesis and regulates transcriptional elongation of erythroid genes

Transcriptional regulators play critical roles in the regulation of cell fate during hematopoiesis. Previous studies in zebrafish have identified an essential role for the transcriptional intermediary factor TIF1 gamma in erythropoiesis by regulating the transcription elongation of erythroid genes. To study if TIF1 gamma plays a similar role in murine erythropoiesis and to assess its function in other blood lineages, we generated mouse models with hematopoietic deletion of TIF1 gamma. Our results showed a block in erythroid maturation in the bone marrow following tif1 gamma deletion that was compensated with enhanced spleen erythropoiesis. Further analyses revealed a defect in transcription elongation of erythroid genes in the bone marrow. In addition, loss of TIF1 gamma resulted in defects in other blood compartments, including a profound loss of B cells, a dramatic expansion of granulocytes and decreased HSC function. TIF1 gamma exerts its functions in a cell-autonomous manner as revealed by competitive transplantation experiments. Our study therefore demonstrates that TIF1 gamma plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved. Published by Elsevier Inc.