Ablation of Nrf2 function does not increase the erythroid or megakaryocytic cell lineage dysfunction caused by p45 NF-E2 gene disruption.
Maf recognition elements (MAREs or NF-E2 binding sites) have been shown to be vital for erythroid- and megakaryocyte-specific gene expression. Transcription factor NF-E2 is composed of p45, a large subunit belonging to the CNC family proteins, and a small Maf subunit, and is thought to activate transcription through its binding to MAREs in both the erythroid and megakaryocytic cell lineages. While p45 gene knockout mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes, and the mutant mice die of massive bleeding within a week after birth, anemia is not apparent in these animals. Disruption of the nrf2 gene, encoding another CNC family protein, results in no hematological abnormalities. We have therefore tested the hypothesis that Nrf2 might compensate for the p45 deficiency in erythroid lineage cells of p45-knockout mice, thereby masking the anticipated anemia. However, we failed to detect any greater failure in either erythroid or megakaryocytic cell development in Nrf2 plus p45 compound mutant mice as compared to with either individual homozygous mutation. These data suggest that p45 and Nrf2 may both be dispensable for hematopoietic cell development, and that other factors regulate erythroid- and megakaryocyte-specific gene expression through their required MAREs.
Kuroha
T
T
Institute of Basic Medical Sciences and Center for TARA, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305, Japan.
Takahashi
S
S
Komeno
T
T
Itoh
K
K
Nagasawa
T
T
Yamamoto
M
M
D000740:Anemia / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004912:Erythrocytes / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics; D006720:Homozygote; D008099:Liver / Q000166:cytology; D008533:Megakaryocytes / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D051267:NF-E2-Related Factor 2; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D051267:NF-E2-Related Factor 2; C494693:Nfe2 protein, mouse; C495636:Nfe2l2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D005914:Globins