Both nuclear factor erythroid 2 45 kDa subunit (p45) and BTB and CNC homolog 1 
(Bach) transcription factors can form dimers with one of the small Maf proteins, 
and these heterodimers bind to the musculoaponeurotic fibrosarcoma oncogene 
(Maf) recognition element (MARE). MARE is known to act as a critical 
cis-regulatory element of erythroid and megakaryocytic genes. Although detailed 
analyses of p45-null mutant mice and small maf compound mutant mice revealed 
that these factors are both critical for platelet production, the functional 
contributions of Bach1 and the relationship or redundancy between Bach1 and p45 
in megakaryocytes remain to be clarified. To address these issues, we generated 
transgenic lines of mice bearing human BACH1 cDNA under the control of the 
GATA-1 locus hematopoietic regulatory domain. The transgenic mouse lines showed 
significant thrombocytopenia associated with impaired maturation of the 
megakaryocytes, and they developed myelofibrosis. The megakaryocytes in the 
transgenic mice exhibited reduced proplatelet formation, and the modal ploidy 
class of megakaryocytes was 2N, indicating the impairment of endomitosis. 
Transcription of the p45 target genes was down-regulated and we indeed found 
that BACH1 binds to the thromboxane synthase gene, one of the target genes for 
p45 in megakaryocytes. These findings thus provide evidence that BACH1 acts as a 
transcriptional repressor in the regulation of MARE-dependent genes in 
megakaryocytes.