Human MafG is a functional partner for p45 NF-E2 in activating globin gene expression.
Mammalian globin gene expression is activated through NF-E2 elements recognized by basic-leucine zipper proteins of the AP-1 superfamily. The specificity of NF-E2 DNA binding is determined by several nucleotides adjacent to a core AP-1 motif, comprising a recognition site for transcription factors of the Maf subfamily. Earlier work proposed that p18(MafK) forms a heterodimer with hematopoietic-specific protein p45 NF-E2 to activate transcription through NF-E2 sites. However, there was no direct evidence that p18(MafK) serves this function in vivo; in fact, mice lacking p18(MafK) have no phenotype. Here we describe a novel cDNA clone that encodes the human homolog of chicken MafG. Human MafG heterodimerizes with p45 NF-E2 and binds DNA with specificity identical to that of purified NF-E2 DNA binding activity. A tethered heterodimer of p45 and MafG is fully functional in supporting expression of alpha- and beta-globin, and in promoting erythroid differentiation in CB3, a p45-deficient mouse erythroleukemia cell line. These results indicate that human MafG can serve as a functional partner for p45 NF-E2, and suggest that the p45/MafG heterodimer plays a role in the regulation of erythropoiesis.
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Howard Hughes Medical Institute, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Kim
M J
MJ
Andrews
N C
NC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D019281:Dimerization; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006801:Humans; D051259:MafG Transcription Factor; D050985:MafK Transcription Factor; D051379:Mice; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C103944:MAFG protein, human; C494695:MAFK protein, human; D051259:MafG Transcription Factor; D050985:MafK Transcription Factor; C491247:Mafg protein, mouse; C494696:Mafk protein, mouse; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; C494693:Nfe2 protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D005914:Globins