Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG.
GATA transcription factors are required for the differentiation of diverse cell types in several species. Recent evidence suggests that their biologic activities may be modulated through interaction with multitype zinc finger proteins, such as Friend of GATA-1 (FOG) and U-shaped (Ush). In cell culture, FOG cooperates with the hematopoietic transcription factor GATA-1 to promote erythroid and megakaryocytic differentiation. We show here that mice lacking FOG die during mid-embryonic development with severe anemia. FOG-/- erythroid cells display a marked, but partial, blockage of maturation, reminiscent of GATA-1- erythroid precursors. In contrast to GATA-1 deficiency, however, megakaryocytes fail to develop in the absence of FOG. Although the FOG-/- erythroid phenotype supports the proposed role of FOG as a GATA-1 cofactor in vivo, the latter finding points to a pivotal, GATA-1-independent requirement for FOG in megakaryocyte development from the bipotential erythroid/megakaryocytic progenitor. We speculate that FOG and other FOG-like proteins serve as complex cofactors that act through both GATA-dependent and GATA-independent mechanisms.
Tsang
A P
AP
Division of Hematology-Oncology, Children's Hospital and Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Fujiwara
Y
Y
Hom
D B
DB
Orkin
S H
SH
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D005314:Embryonic and Fetal Development; D015672:Erythroid Precursor Cells; D004920:Erythropoiesis / Q000502:physiology*; D017353:Gene Deletion; D018390:Gene Targeting; D006410:Hematopoiesis / Q000502:physiology*; D008533:Megakaryocytes / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors
D002352:Carrier Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse