Isolation and characterization of zebrafish NFE2.
Vertebrate hematopoiesis is regulated by distinct cell-specific transcription factors such as GATA-1 and SCL. Mammalian p45-NFE2 was characterized for its ability to bind the hypersensitive sites of the globin locus control region. NFE2 is a member of a cap'n'collar (CNC) and basic zipper (BZIP) superfamily that regulates gene transcription. It has been implicated in diverse processes such as globin gene expression, oxidative stress, and platelet lineage differentiation. Here, we have isolated the zebrafish ortholog of NFE2. The gene is highly homologous, particularly in the DNA-binding domain. Mapping the zebrafish NFE2 to linkage group 23 establishes a region of chromosomal synteny with human chromosome 12, further suggesting evolutionary conservation. During embryogenesis, the zebrafish gene is expressed specifically in erythroid cells and also in the developing ear. NFE2 expression is lacking in zebrafish mutants that have no hematopoietic cells. An analysis of the sauternes mutant, which carries a mutation in the ALAS-2 gene and thus has defective heme synthesis, demonstrates higher levels of NFE2 expression than normal. This further establishes the block to erythroid differentiation in the sauternes mutant. Our studies demonstrate conservation of the vertebrate genetic program for the erythroid lineage.
Pratt
Stephen J
SJ
Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Drejer
Anna
A
Foott
Helen
H
Barut
Bruce
B
Brownlie
Alison
A
Postlethwait
John
J
Kato
Yasutake
Y
Yamamoto
Masayuki
M
Zon
Leonard I
LI
D000818:Animals; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D050984:NF-E2 Transcription Factor, p45 Subunit; D026801:Synteny / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050984:NF-E2 Transcription Factor, p45 Subunit; D014157:Transcription Factors; D029961:Zebrafish Proteins; C494694:nfe2 protein, zebrafish