徳島大学 教育・研究者情報データベース(EDB)

1. 田原 強([徳島大学.先端研究推進センター.バイオイメージング研究部門])

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2. (英) Sun Jiying

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3. (英) Igarashi Kazuhiko

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4. (英) Taketani Shigeru

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(英) Heme-dependent up-regulation of the alpha-globin gene expression by transcriptional repressor Bach1 in erythroid cells.

(英) The transcriptional factor Bach1 forms a heterodimer with small Maf family, and functions as a repressor of the Maf recognition element (MARE) in vivo. To investigate the involvement of Bach1 in the heme-dependent regulation of the expression of the alpha-globin gene, human erythroleukemia K562 cells were cultured with succinylacetone (SA), a heme biosynthetic inhibitor, and the level of alpha-globin mRNA was examined. A decrease of alpha-globin mRNA was observed in SA-treated cells, which was restored by the addition of hemin. The heme-dependent expression of alpha-globin occurred at the transcriptional level since the expression of human alpha-globin gene promoter-reporter gene containing hypersensitive site-40 (HS-40) was decreased when K562 cells were cultured with SA. Hemin treatment restored the decrease of the promoter activity by SA. The regulation of the HS-40 activity by heme was dependent on the NF-E2/AP-1 (NA) site, which is similar to MARE. The NA site-binding activity of Bach1 in K562 increased upon SA-treatment, and the increase was diminished by the addition of hemin. The transient expression of Bach1 and mutated Bach1 lacking CP motifs suppressed the HS-40 activity, and cancellation of the repressor activity by hemin was observed when wild-type Bach1 was expressed. The expression of NF-E2 strengthened the restoration of the Bach1-effect by hemin. Interestingly, nuclear localization of Bach1 increased when cells were treated with SA, while hemin induced the nuclear export of Bach1. These results indicated that heme plays an important role in the induction of alpha-globin gene expression through disrupting the interaction of Bach1 and the NA site in HS-40 enhancer in erythroid cells.

1. (英) Animals
2. (英) Basic-Leucine Zipper Transcription Factors
3. (英) Cell Nucleus
4. (英) DNA-Binding Proteins
5. (英) Enhancer Elements, Genetic
6. (英) Enzyme Inhibitors
7. (英) Erythroid Cells
8. (英) Erythroid-Specific DNA-Binding Factors
9. (英) Fanconi Anemia Complementation Group Proteins
10. (英) Gene Expression Regulation
11. (英) Genes, Reporter
12. (英) Globins
13. (英) Heme
14. (英) Hemin
15. (英) Heptanoates
16. (英) Humans
17. (英) K562 Cells
18. (英) Mice
19. (英) Multigene Family
20. (英) NF-E2 Transcription Factor
21. (英) NF-E2 Transcription Factor, p45 Subunit
22. (英) Promoter Regions, Genetic
23. (英) Transcription Factors
24. (英) Transcription, Genetic
25. (英) Up-Regulation

1. (英) PublicationType: Journal Article

2. (英) PublicationType: Research Support, Non-U.S. Gov't