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PMID: 12077323 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 14 ·2002-07-09 ·Pages 9237-42

Chang AN, Cantor AB, Fujiwara Y, Lodish MB, Droho S, Crispino JD, Orkin SH

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-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.

MeSH Terms
Amino Acid Sequence Amino Acid Substitution Animals Base Sequence Carrier Proteins/physiology DNA-Binding Proteins/chemistry,genetics,physiology Erythroid-Specific DNA-Binding Factors Female GATA1 Transcription Factor GATA2 Transcription Factor Hematopoiesis/physiology Male Megakaryocytes/cytology,physiology Mice Mice, Inbred C57BL Mice, Knockout Mice, Mutant Strains Mice, Transgenic Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/physiology Transcription Factors/chemistry,genetics,physiology Zinc Fingers/physiology
Chemicals
Carrier Proteins DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor GATA2 Transcription Factor Gata1 protein, mouse Gata2 protein, mouse Nuclear Proteins Transcription Factors Zfpm1 protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Chang Aaron N
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
Fujiwara Yuko
Lodish Maya B
Droho Steven
Crispino John D
Orkin Stuart H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.142302099
Published
2002-07-09
Epub
2002-00-20
Pages
9237-42
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC123124
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.142302099 PMC Full Text View journal details
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