Regulation of hematopoiesis by the transcription factors Bach1 and Bach2

转录因子 Bach1 和 Bach2 调节造血作用

• 批准号: 15390095
• 负责人: IGARASHI Kazuhiko
• 金额: $ 9.54万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390095/
• 关键词: Bach1; Bach2; transcription factor; globin; B cell; heme; oxidative stress; Maf

For the sake of clarity, I shall give a summary of the analysis of B cell system below.Activated B cells differentiate to plasma cells to secrete immunoglobulin MI (IgM) or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins. Diversification of antibody function by CSR is important for humoral immunity. However, it remains unclear how the decision for the bifurcation is made. Bach2 is a B cell-specific transcription repressor interacting with the small Maf proteins whose expression is high only prior to plasma cell stage. Here we report that Bach2 is critical for CSR and somatic hypermutation (SHM) of immunoglobulin genes. Genetic ablation of bach2 in mice revealed that Bach2 was required for both T cell-independent and -dependent IgG responses and SHM. When stimulated in vitro, Bach2-deficient B cells produced IgM as did wild-type cells and expressed abundantly Blimp-1 and XBP-1, critical regulators of the plasmacytic differentiation, suggesting that Bach2 was not required for the plasmacytic differentiation per se. However, they failed to undergo efficient CSR. These findings define Bach2 as a key regulator of antibody response and provide an insight into the orchestration of CSR and SHM during plasma cell differentiation.

为了清楚起见，我将摘要下面的B细胞系统分析。激活的B细胞与浆细胞分开，以分泌免疫球蛋白MI（IGM），或者在接受类开关重组（CSR）（CSR）后，分泌其他免疫球蛋白类别。 CSR对抗体功能的多样化对于体液免疫很重要。但是，尚不清楚如何做出分叉的决定。 Bach2是B细胞特异性转录阻遏物，与小型MAF蛋白相互作用，其表达仅在浆细胞阶段之前才能表达高。在这里，我们报告说，Bach2对于免疫球蛋白基因的CSR和体细胞超突变（SHM）至关重要。 Bach2在小鼠中的遗传消融表明，T细胞独立和依赖性IgG反应和SHM都需要Bach2。当在体外刺激时，Bach2缺陷型B细胞会像野生型细胞一样产生IgM，并表达了纤溶实性分化的关键调节剂，表达了大量的Blimp-1和XBP-1，这表明Bach2不是浆化性分化的必需。但是，他们未能经历有效的CSR。这些发现将BACH2定义为抗体反应的关键调节剂，并提供了浆细胞分化过程中CSR和SHM编排的洞察力。

项目成果

Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1

• DOI: 10.1038/sj.emboj.7600248
• 发表时间: 2004-07-07
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Suzuki, H;Tashiro, S;Igarashi, K
• 通讯作者: Igarashi, K

Tashiro, S.: "Repression of PML nuclear body-associated transcription by oxidative stress-activated Bach2"Mol.Cell.Biol.. (in press). (2004)

Tashiro, S.：“氧化应激激活的 Bach2 对 PML 核体相关转录的抑制”Mol.Cell.Biol..（出版中）。

Suzuki, H.: "Cadmium induces nuclear export of Bach1, a transcriptional repressor of heme oxygenase-1 gene"J.Biol.Chem.. 278. 49246-49253 (2003)

Suzuki, H.：“镉诱导 Bach1 的核输出，Bach1 是血红素加氧酶-1 基因的转录抑制因子”J.Biol.Chem.. 278. 49246-49253 (2003)

Heme positively regulates the expression of b-globin at the locus control region via the transcription factor Bach1 in erythroid cells.

血红素通过红系细胞中的转录因子 Bach1 正向调节基因座控制区 b-珠蛋白的表达。

• 发表时间: 2004
• 期刊: J.Biol.Chem. 279
• 作者: Tahara;T.
• 通讯作者: T.

Brand, M.: "Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics"Nature Struct.Mol.Biol.. 11. 73-80 (2004)

Brand, M.：“定量蛋白质组学揭示红细胞分化过程中转录因子复合物的动态变化”Nature Struct.Mol.Biol.. 11. 73-80 (2004)