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

Xiaoying Bai, Jennifer J. Trowbridge, Elizabeth Riley, Joseph A. Lee, Anthony DiBiase, Vesa M. Kaartinen, Stuart H. Orkin, Leonard I. Zon

Research output: Contribution to journalArticle

21 Scopus citations

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 TIF1γ in erythropoiesis by regulating the transcription elongation of erythroid genes. To study if TIF1γ plays a similar role in murine erythropoiesis and to assess its function in other blood lineages, we generated mouse models with hematopoietic deletion of TIF1γ. Our results showed a block in erythroid maturation in the bone marrow following tif1γ 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 TIF1γ resulted in defects in other blood compartments, including a profound loss of B cells, a dramatic expansion of granulocytes and decreased HSC function. TIF1γ exerts its functions in a cell-autonomous manner as revealed by competitive transplantation experiments. Our study therefore demonstrates that TIF1γ plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved.

Original languageEnglish (US)
Pages (from-to)422-430
Number of pages9
JournalDevelopmental Biology
Volume373
Issue number2
DOIs
StatePublished - Jan 15 2013

Keywords

  • Hematopoiesis
  • Lineage differentiation
  • Transcription elongation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Bai, X., Trowbridge, J. J., Riley, E., Lee, J. A., DiBiase, A., Kaartinen, V. M., Orkin, S. H., & Zon, L. I. (2013). TiF1-gamma plays an essential role in murine hematopoiesis and regulates transcriptional elongation of erythroid genes. Developmental Biology, 373(2), 422-430. https://doi.org/10.1016/j.ydbio.2012.10.008