Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-2.
GATA-2 is a zinc finger transcription factor essential for differentiation of immature hematopoietic cells. We analyzed the function of GATA-2 by a combined method of tetracycline-dependent conditional gene expression and in vitro hematopoietic differentiation from mouse embryonic stem (ES) cells using OP9 stroma cells (OP9 system). In the presence of macrophage colony-stimulating factor (M-CSF), the OP9 system induced macrophage differentiation. GATA-2 expression in this system inhibited macrophage differentiation and redirected the fate of hematopoietic differentiation to other hematopoietic lineages. GATA-2 expression commencing at day 5 or day 6 induced megakaryocytic or erythroid differentiation, respectively. Expression levels of PU.1, a hematopoietic transcription factor that interferes with GATA-2, appeared to play a critical role in differentiation to megakaryocytic or erythroid lineages. Transcription of PU.1 was affected by histone acetylation induced by binding of GATA-2 to the PU.1 promoter region. This study demonstrates that the function of GATA-2 is modified in a context-dependent manner by expression of PU.1, which in turn is regulated by GATA-2.
Kitajima
Kenji
K
Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University, Yamada-oka 2-2, Suita, Osaka 565-0871, Japan.
Tanaka
Makoto
M
Zheng
Jie
J
Yen
Hilo
H
Sato
Ayuko
A
Sugiyama
Daijiro
D
Umehara
Hiroki
H
Sakai
Eiko
E
Nakano
Toru
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology; D051379:Mice; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D013752:Tetracycline / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D000099232:Proto-Oncogene Protein Spi-1
D000900:Anti-Bacterial Agents; D050989:GATA2 Transcription Factor; D011518:Proto-Oncogene Proteins; D013752:Tetracycline; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C494712:Gata2 protein, mouse