GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis

Aaron N. Chang, Alan B. Cantor, Yuko Fujiwara, Maya B. Lodish, Steven Droho, John D. Crispino, Stuart H. Orkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

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-1KI (GATA-1 is located on the X-chromosome) or GATA-2KI/KI mice, compound GATA-1KI GATA-2KI/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.

Original languageEnglish (US)
Pages (from-to)9237-9242
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number14
DOIs
StatePublished - Jul 9 2002

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis'. Together they form a unique fingerprint.

Cite this