...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dual role for the methyltransferase G9a in the maintenance of β-globin gene transcription in adult erythroid cells
【24h】

Dual role for the methyltransferase G9a in the maintenance of β-globin gene transcription in adult erythroid cells

机译:甲基转移酶G9a在维持成年红系细胞β珠蛋白基因转录中的双重作用

获取原文
获取原文并翻译 | 示例
           

摘要

Using a proteomics screen, we have identified the methyltransferase G9a as an interacting partner of the hematopoietic activator NF-E2. We show that G9a is recruited to the β-globin locus in a NF-E2-dependent manner and spreads over the entire locus. While G9a is often regarded as a corepressor, knocking down this protein in differentiating adult erythroid cells leads to repression of the adult β~(maj) globin gene and aberrant reactivation of the embryonic β-like globin gene E~y. While in adult cells G9a maintains E~y in a repressed state via dimethylation of histone H3 at lysines 9 and 27, it activates β~(maj) transcription in a methyltransferase-independent manner. Interestingly, the demethylase UTX is recruited to the β~(maj) (but not the E~y) promoter where it antagonizes G9a-dependent H3K27 dimethylation. Collectively, these results reveal a dual role for G9a in maintaining proper expression (both repression and activation) of the β-globin genes in differentiating adult erythroid cells.
机译:使用蛋白质组学筛选,我们已确定甲基转移酶G9a为造血激活因子NF-E2的相互作用伴侣。我们显示,G9a以NF-E2依赖的方式被募集到β-珠蛋白基因座,并分布在整个基因座上。虽然G9a通常被认为是一个核心抑制剂,但在分化成年红细胞的过程中将其击倒会导致成年β_(maj)球蛋白基因的阻遏和胚胎β样球蛋白基因E〜y的异常激活。在成体细胞中,G9a通过赖氨酸9和27处组蛋白H3的二甲基化使Ey维持在抑制状态,但它以不依赖甲基转移酶的方式激活β〜(maj)转录。有趣的是,脱甲基酶UTX被募集到β_(maj)(而不是E_y)启动子上,在那里它拮抗G9a依赖的H3K27二甲基化。总的来说,这些结果揭示了G9a在分化成年红系细胞中维持β-珠蛋白基因的正确表达(抑制和激活)中的双重作用。

著录项

  • 来源
  • 作者单位

    The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada K1H 8L6;

    The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada K1H 8L6;

    The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada K1H 8L6;

    The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada K1H 8L6;

    Dana-Farber Cancer Institute, Boston, MA 02115;

    Institute for Systems Biology, Seattle, WA 98103;

    The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada K1H 8L6 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6;

    The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada K1H 8L6 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    chromatin; histone methylation; UTX; NF-E2;

    机译:染色质组蛋白甲基化UTX;NF-E2;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号