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

ABSTRACT: 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? in erythropoiesis by regulating the transcription elongation of erythroid genes. To study if TIF1? 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?. Our results showed a block in erythroid maturation in the bone marrow following tif1? 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? resulted in defects in other blood compartments, including a profound loss of B cells, a dramatic expansion of granulocytes and decreased HSC function. TIF1? exerts its functions in a cell-autonomous manner as revealed by competitive transplantation experiments. Our study therefore demonstrates that TIF1? plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved.

SUBMITTER: Bai X 

PROVIDER: S-EPMC3540997 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature