title: NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development.
abstract: The locus control region of the beta-globin gene is composed of four erythroid-specific hypersensitive sites. Hypersensitive site 2 has been shown to be a powerful enhancer and contains a tandem repeat sequence for the transcription factors AP1 and NFE2 (activating protein 1 and nuclear factor erythroid 2, respectively). The human NRF2 (NFE2 related factor 2) has been isolated by bacterial expression screening using this core sequence as a probe. p45-NFE2, NRF1, and NRF2 belong to the CNC ("cap 'n' collar") subfamily of the basic region-leucine zipper transcription factors, which exhibits strong homology at specific regions such as the "CNC" and the DNA binding and leucine zipper domains. Although the erythroid-specific p45-NFE2 has been implicated in globin gene regulation, p45-NFE2 null mice succumb to bleedings due to lack of platelets and those that survive exhibit only a mild anemia. To determine the function of NRF2, which we found to be widely expressed in vivo, we have characterized the genomic structure of the mouse NRF2 gene, disrupted the Nrf2 gene by homologous recombination in mouse embryonic stem cells (ES cells), and generated NRF2-/- mice. Homozygous mutant mice developed normally, were not anemic, reached adulthood, and reproduced. Our studies indicate that NRF2 is dispensable for mouse development.
authors.affiliation: Institute of Molecular Biology, University of Hong Kong, Hong Kong.
authors.forename: K
authors.initials: K
authors.lastname: Chan
authors.forename: R
authors.initials: R
authors.lastname: Lu
authors.forename: J C
authors.initials: JC
authors.lastname: Chang
authors.forename: Y W
authors.initials: YW
authors.lastname: Kan
mesh_terms: D000375:Aging / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D005314:Embryonic and Fetal Development; D004920:Erythropoiesis; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D006801:Humans; D016350:Leucine Zippers; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D051267:NF-E2-Related Factor 2; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells; D015534:Trans-Activators / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors