title: 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 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.
authors.affiliation: Stem Cell Program, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Bai
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Trowbridge
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Riley
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lee
authors.forename: Anthony
authors.initials: A
authors.lastname: DiBiase
authors.forename: Vesa M
authors.initials: VM
authors.lastname: Kaartinen
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038042:Myelopoiesis / Q000235:genetics; D013154:Spleen / Q000378:metabolism; D061805:Transcription Elongation, Genetic; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; C491420:Trim33 protein, mouse