Regulation of erythropoiesis and macrophages by the heme signal
Description: We reported previously that heme binds to the transcription factors Bach1 and Bach2 to regulate gene expression. In this study, we have successfully established the regulatory roles and biological significances of the heme-mediated regulation of these transcription factors.We found that, unlike known heme-binding proteins, the heme-binding region of Bach2 is structurally disordered, and that this region remained disordered even in the presence of heme. Nonetheless, heme induced an interaction of Bach2 and protein kinase, which then phosphorylated Bach2. We also found that Bach1 was critical for adaptation of erythroid cells to iron deficiency. Bach1 kept expression of key erythroid transcription factor genes under such conditions. In stem and progenitor cells, Bach2 and Bach1 were found to promote lymphoid cell differentiation by restricting the expression of myeloid transcription factors as well as their target genes important for myeloid cell differentiation.
Amount: ¥46,280,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (A)
Start date: 2015-04-01
End date: 2018-03-31
Investigator: Kazuhiko IGARASHI
Institution: Tohoku University
Funded outputs count: 29
Funder award ID: 15H02506
OpenAlex ID: G4494078986