GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis.
The function of GATA transcription factors in diverse developmental contexts depends in part on physical interaction with cofactors of the Friend of GATA (FOG) family. However, previous studies indicate that FOG-1 may play a GATA-1-independent role in early megakaryopoiesis, suggesting that FOG proteins might act in a GATA factor-independent manner. Here, we have generated mouse knock-in (KI) mutants harboring a critical valine-to-glycine substitution in the amino-terminal zinc fingers of GATA-1 and GATA-2 to ablate FOG interaction. In contrast to male GATA-1(KI) (GATA-1 is located on the X-chromosome) or GATA-2(KI/KI) mice, compound GATA-1(KI) GATA-2(KI/KI) mutant mice display complete megakaryopoietic failure, a phenocopy of FOG-1(-/-) mice. We conclude that FOG-1 requires an interaction with either GATA-1 or -2 as part of its essential role in early megakaryopoiesis. On the basis of these and previous reports, we infer that GATA factor dependence is a critical aspect of FOG protein function.
Chang
Aaron N
AN
Division of Hematology-Oncology, Children's Hospital and Dana-Farber Cancer Institute and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Cantor
Alan B
AB
Fujiwara
Yuko
Y
Lodish
Maya B
MB
Droho
Steven
S
Crispino
John D
JD
Orkin
Stuart H
SH
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D006410:Hematopoiesis / Q000502:physiology*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016335:Zinc Fingers / Q000502:physiology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse