Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1
Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1
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DOI：
10.1093/emboj/20.11.2835
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发表时间：
2001-06-01
期刊：
影响因子：
11.4
通讯作者：
Igarashi, K
中科院分区：
文献类型：
--
作者：
Ogawa, K;Sun, J;Igarashi, K
血红素控制参与球蛋白和血红素合成的基因的表达。哺乳动物转录因子Bach 1通过与小Maf家族蛋白形成拮抗性异源寡聚体而作为Maf识别元件（MARE）的阻遏物起作用。我们在这里表明，血红素特异性结合Bach 1和调节其DNA阻碍活性。缺失研究表明，Bach 1的血红素结合区域被限制在其C-末端区域，具有四个二肽半胱氨酸-脯氨酸（CP）基序。Bach 1的所有CP基序中的突变消除了其与血红素的相互作用。在凝胶迁移率变动分析中，Bach 1作为MafK异源寡聚体的DNA结合活性被血红素显著抑制。在转染细胞中加入氯化血红素后，Bach 1的阻遏物活性丧失。这些结果表明，增加的血红素水平抑制阻遏物Bach 1，导致诱导大量具有MARE的基因。
Heme controls expression of genes involved in the synthesis of globins and heme, The mammalian transcription factor Bach1 functions as a repressor of the Maf recognition element (MARE) by forming antagonizing hetero-oligomers with the small Maf family proteins. We show here that heme binds specifically to Bach1 and regulates its DNA-hinding activity. Deletion studies demonstrated that a heme-binding region of Bach1 is confined within its C-terminal region that possesses four dipeptide cysteine-proline (CP) motifs. Mutations in all of the CP motifs of Bach1 abolished its interaction with heme. The DNA-binding activity of Bach1 as a MafK hetero-oligomer was markedly inhibited by heme in gel mobility shift assays. The repressor activity of Bach1 was lost upon addition of hemin in transfected cells, These results suggest that increased levels of heme inactivate the repressor Bach1, resulting in induction of a host of genes with MAREs.