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

Hozumi Motohashi, Fumiki Katsuoka, Jordan A. Shavit, James Douglas Engel, Masayuki Yamamoto

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The small Maf transcription factor proteins bind to Maf Recognition Elements (MAREs) by dimerizing with CNC proteins or themselves. We undertook experiments to clarify the functional relationship between the small Mafs and their partners in vivo. Embryos expressing abundant transgene-derived MafK died of severe anemia, while lines expressing lower levels of small Maf lived to adulthood. Megakaryocytes from the latter overexpressing lines exhibited reduced proplatelet formation and MARE-dependent transcription, phenocopying mafG null mutant mice. When the mafG null mutants were bred to small Maf-overexpressing transgenic animals, both loss- and gain-of-function phenotypes were reversed. These results provide direct in vivo evidence that transcriptional regulation through MARE elements hinges on an exquisitely sensitive balance of activating CNC molecules and their small Maf partners.

Original languageEnglish
Pages (from-to)865-876
Number of pages12
JournalCell
Volume103
Issue number6
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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