Iron-heme-Bach1 axis is involved in erythroblast adaptation to iron deficiency

Masahiro Kobayashi, Hiroki Kato, Hiroshi Hada, Ari Itoh-Nakadai, Tohru Fujiwara, Akihiko Muto, Yukihiro Inoguchi, Kenji Ichiyanagi, Wataru Hojo, Naohisa Tomosugi, Hiroyuki Sasaki, Hideo Harigae, Kazuhiko Igarashi

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    Iron plays the central role in oxygen transport by erythrocytes as a constituent of heme and hemoglobin. The importance of iron and heme is also to be found in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is deactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1–/– mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1–/– mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme- Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin.

    Original languageEnglish
    Pages (from-to)454-465
    Number of pages12
    JournalHaematologica
    Volume102
    Issue number3
    DOIs
    Publication statusPublished - Feb 28 2017

    All Science Journal Classification (ASJC) codes

    • Hematology

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