Molecular cloning and functional characterization of a new Cap'n' collar family transcription factor Nrf3

The NF-E2-binding sites or Maf recognition elements (MARE) are essential ci s-acting elements in the regulatory regions of erythroid-specific genes rec ognized by the erythroid transcription factor NF-E2, composed of p45 and Ma fK. Recently, two p45-related factors Nrf1 and Nrf2 were isolated, and they are now collectively grouped as the Cap'n' collar (CNC) family. CNC factor s bind to MARE through heterodimer formation with small Maf proteins. We re port here the identification and characterization of a novel CNC factor, Nr f3, encoding a predicted 73-kDa protein with a basic region-leucine zipper domain highly homologous to those of other CNC proteins. In vitro and in vi vo analyses showed that Nrf3 can heterodimerize with MafK and that this com plex binds to the MARE in the chicken beta-globin enhancer and can activate transcription. Nrf3 mRNA is highly expressed in human placenta and B cell and monocyte lineage. Chromosomal localization of human Nrf3 is 7p14-15, wh ich lies near the hoxA gene locus. As the genetic loci of p45, nrf1, and nr f2 have been mapped close to those of hoxC, hoxB, and hoxD, respectively, t he present study strongly argues for the idea that a single ancestral gene for the CNC family members may have been localized near the ancestral Hox c luster and have diverged to give rise to four closely related CNC factors t hrough chromosome duplication.