GATA-4 incompletely substitutes for GATA-1 in promoting both primitive and definitive erythropoiesis in vivo.
Vertebrate GATA transcription factors have been classified into two subgroups; GATA-1, GATA-2, and GATA-3 are expressed in hematopoietic cells, whereas GATA-4, GATA-5, and GATA-6 are expressed in mesoendoderm-derived tissues. We previously discovered that expression of GATA-2 or GATA-3 under the transcriptional control for the Gata1 gene eliminates lethal anemia in Gata1 germ line mutant mice (Gata1.05/Y). Here, we show that the GATA-4 expression by the same regulatory cassette prolongs the life span of Gata1.05/Y embryos from embryonic day 12.5 to 15.5 but fails to abrogate its embryonic lethality. Gata1.05/Y mice bearing the GATA-4 transgene showed impaired maturation of both primitive and definitive erythroid cells and defective erythroid cell expansion in fetal liver. Moreover, the incidence of apoptosis was observed prominently in primitive erythroid cells. In contrast, a GATA-4-GATA-1 chimeric protein prepared by linking the N-terminal region of GATA-4 to the C-terminal region of GATA-1 significantly promoted the differentiation and survival of primitive erythroid cells, although this protein is still insufficient for rescuing Gata1.05/Y embryos from lethal anemia. These data thus show a functional incompatibility between hematopoietic and endodermal GATA factors in vivo and provide evidence indicating specific roles of the C-terminal region of GATA-1 in primitive erythropoiesis.
Hosoya-Ohmura
Sakie
S
Graduate School of Comprehensive Human Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba 305-8577, Japan.
Mochizuki
Naomi
N
Suzuki
Mikiko
M
Ohneda
Osamu
O
Ohneda
Kinuko
K
Yamamoto
Masayuki
M
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D004920:Erythropoiesis / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010957:Plasmids; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
D050982:GATA1 Transcription Factor; D050991:GATA4 Transcription Factor; C494689:Gata1 protein, mouse