Growth Factor Independence 1b (Gfi1b) Is Important for the Maturation of Erythroid Cells and the Regulation of Embryonic Globin Expression

• DOI: 10.1371/journal.pone.0096636
• Publication Date: 2014-05-06T20:43:58Z
• Authors: Lothar Vassen; Hugues Beauchemin; Wafaa Lemsaddek; Joseph Krongold; Marie Trudel; Tarik Möröy
• Keywords: Erythropoietin receptor

Growth factor independence 1b (GFI1B) is a DNA binding repressor of transcription with vital functions in hematopoiesis. Gfi1b-null embryos die at midgestation very likely due to defects erythro- and megakaryopoiesis. To analyze the full functionality Gfi1b, we used conditionally deficient mice that harbor floxed Gfi1b alleles inducible (Mx-Cre, Cre-ERT) or erythroid specific (EpoR-Cre) Cre expressing transgenes. In contrast germline knockout, EpoR-Cre mediated ablation allows gestation, but causes perinatal lethality few surviving adulthood. Both embryonic deletion by adult Mx-Cre Cre-ERT leads reduced numbers precursors, perturbed delayed maturation, anemia extramedullary erythropoiesis. Global expression analyses showed Hba-x, Hbb-bh1 Hbb-y globin genes were upregulated TER119+ fetal liver cells over gestation period from day 12.5–17.5 p.c. an increased level gene was even maintained mice. While Bcl11a, regulator not affected deficiency, Gata1 Sox6, also involved switch, almost entirely lost when absent. These findings establish as maturation.