Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins.
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.
Motohashi
H
H
Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences University of Tsukuba 1-1-1 Tennoudai 305-8577, Tsukuba, Japan.
Katsuoka
F
F
Shavit
J A
JA
Engel
J D
JD
Yamamoto
M
M
D016475:3T3 Cells; D000740:Anemia / Q000235:genetics; D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D019281:Dimerization; D004622:Embryo, Mammalian; D004920:Erythropoiesis; D018703:Founder Effect; D018628:Gene Dosage; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006410:Hematopoiesis; D015151:Immunoblotting; D007150:Immunohistochemistry; D016350:Leucine Zippers / Q000235:genetics; D050985:MafK Transcription Factor; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D050985:MafK Transcription Factor; D009687:Nuclear Proteins