Erythroid maturation and globin gene expression in mice with combined deficiency of NF-E2 and nrf-2.
NF-E2 binding sites, located in distant regulatory sequences, may be important for high level alpha- and beta-globin gene expression. Surprisingly, targeted disruption of each subunit of NF-E2 has either little or no effect on erythroid maturation in mice. For p18 NF-E2, this lack of effect is due, at least in part, to the presence of redundant proteins. For p45 NF-E2, one possibility is that NF-E2-related factors, Nrf-1 or Nrf-2, activate globin gene expression in the absence of NF-E2. To test this hypothesis for Nrf-2, we disrupted the Nrf-2 gene by homologous recombination. Nrf-2-deficient mice had no detectable hematopoietic defect. In addition, no evidence was found for reciprocal upregulation of NF-E2 or Nrf-2 protein in fetal liver cells deficient for either factor. Fetal liver cells deficient for both NF-E2 and Nrf-2 expressed normal levels of alpha- and beta-globin. Mature mice with combined deficiency of NF-E2 and Nrf-2 did not exhibit a defect in erythroid maturation beyond that seen with loss of NF-E2 alone. Thus, the presence of a mild erythroid defect in NF-E2-deficient mice is not the result of compensation by Nrf-2.
Martin
F
F
Department of Biochemistry, Saint Jude Children's Research Hospital, Memphis, TN, USA.
van Deursen
J M
JM
Shivdasani
R A
RA
Jackson
C W
CW
Troutman
A G
AG
Ney
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D019281:Dimerization; D015672:Erythroid Precursor Cells / Q000166:cytology; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis; D051268:GA-Binding Protein Transcription Factor; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics*; D050985:MafK Transcription Factor; D051379:Mice; D018345:Mice, Knockout / Q000196:embryology; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D010455:Peptides / Q000276:immunology; D013234:Stem Cells; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D051268:GA-Binding Protein Transcription Factor; C495656:Gabpa protein, mouse; C495658:Gabpb1 protein, mouse; D050985:MafK Transcription Factor; C494696:Mafk protein, mouse; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D010455:Peptides; D014157:Transcription Factors; D005914:Globins