Positive or negative MARE-dependent transcriptional regulation is by the abundance of small Maf proteins

The small Maf transcription factor proteins bind to Maf Recognition Element s (MAREs) by dimerizing with CNC proteins or themselves. We undertook exper iments to clarify the functional relationship between the small Mafs and th eir partners in vivo. Embryos expressing abundant transgene-derived MafK di ed of severe anemia, while lines expressing lower levels of small Maf lived to adulthood. Megakaryocytes from the latter overexpressing lines exhibite d reduced proplatelet formation and MARE-dependent transcription, phenocopy ing mafG null mutant mice. When the mafG null mutants were bred to small Ma f-overexpressing transgenic animals, both loss- and gain-of-function phenot ypes were reversed. These results provide direct in vivo evidence that tran scriptional regulation through MARE elements hinges on an exquisitely sensi tive balance of activating CNC molecules and their small Maf partners.