NF-E2 is a heterodimer consisting of a hematopoietic-specific subunit NFE2-p45, a member of the cap and collar (CNC) family, and a more widely expressed small subunit which can be any of the three small members of the Maf protein family MafF, MafG OR MafK (Motohashi et al. 1997). MafG and MafK are the predominant small Maf molecules in erythroid cells and megakaryocytes (Shavit et al. 1998).
NF-E2 binds to an extended AP-1-like element, TGCTGA(G/C)TCA, which is found in the locus control regions (LCRs) of the alpha- and beta-globin genes and in the promoters of several heme biosynthetic enzyme genes (see Motohashi et al. 1997). NF-E2 binding sites in the DNase I hypersensitive site 2 (HS2) of the beta-globin LCR are essential for its enhancer activity (Ney et al. 1990, Talbot & Grosveld 1991).
NFE2-p45 null mice have a mild defect in globin gene expression, suggesting that other members of the CNC protein family can substitute for function in vivo (Shivdasani & Orkin 1995).