...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Transcriptional regulation of the ferritin heavy-chain gene: the activity of the CCAAT binding factor NF-Y is modulated in heme-treated Friend leukemia cells and during monocyte-to-macrophage differentiation.
【24h】

Transcriptional regulation of the ferritin heavy-chain gene: the activity of the CCAAT binding factor NF-Y is modulated in heme-treated Friend leukemia cells and during monocyte-to-macrophage differentiation.

机译：铁蛋白重链基因的转录调控：CCAAT结合因子NF-Y的活性在血红素处理过的Friend白血病细胞中和单核细胞向巨噬细胞分化过程中受到调节。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The ferritin H-chain gene promoter regulation was analyzed in heme-treated Friend leukemia cells (FLCs) and during monocyte-to-macrophage differentiation. In the majority of cell lines studied, the regulation of ferritin expression was exerted mostly at the translational level. However, in differentiating erythroid cells, which must incorporate high levels of iron to sustain hemoglobin synthesis, and in macrophages, which are involved in iron storage, transcriptional regulation seemed to be a relevant mechanism. We show here that the minimum region of the ferritin H-gene promoter that is able to confer transcriptional regulation by heme in FLCs to a reporter gene is 77 nucleotides upstream of the TATA box. This cis element binds a protein complex referred to as HRF (heme-responsive factor), which is greatly enhanced both in heme-treated FLCs and during monocyte-to-macrophage differentiation. The CCAAT element present in reverse orientation in this promoter region of the ferritin H-chain gene is necessary for binding and for gene activity, since a single point mutation is able to abolish the binding of HRF and the transcriptional activity in transfected cells. By competition experiments and supershift assays, we identified the induced HRF as containing at least the ubiquitous transcription factor NF-Y. NF-Y is formed by three subunits, A, B, and C, all of which are necessary for DNA binding. Cotransfection with a transdominant negative mutant of the NF-YA subunit abolishes the transcriptional activation by heme, indicating that NF-Y plays an essential role in this activation. We have also observed a differential expression of the NF-YA subunit in heme-treated and control FLCs and during monocyte-to-macrophage differentiation.
机译：在血红素治疗的Friend白血病细胞（FLC）和单核细胞向巨噬细胞分化过程中分析了铁蛋白H链基因启动子的调控。在研究的大多数细胞系中，铁蛋白表达的调节主要在翻译水平上起作用。但是，在分化红系细胞（必须掺入高水平的铁以维持血红蛋白合成）和巨噬细胞（参与铁的储存）中，转录调控似乎是一个相关机制。我们在这里显示，能够通过FLCs中的血红素赋予报道基因转录调控的铁蛋白H基因启动子的最小区域是TATA框上游的77个核苷酸。该顺式元件结合称为HRF（血红素响应因子）的蛋白质复合物，该复合物在血红素处理的FLC和单核细胞向巨噬细胞分化过程中均大大增强。在铁蛋白H链基因的该启动子区域以反向定向存在的CCAAT元件对于结合和基因活性是必需的，因为单点突变能够消除HRF的结合和转染细胞中的转录活性。通过竞争实验和超频分析，我们确定诱导的HRF至少包含普遍存在的转录因子NF-Y。 NF-Y由三个亚基A，B和C形成，它们都是DNA结合所必需的。与NF-YA亚基的超显性负突变体共转染消除了血红素的转录激活，表明NF-Y在这种激活中起关键作用。我们还观察到在血红素处理和对照的FLC和单核细胞向巨噬细胞的分化过程中NF-YA亚基的差异表达。

著录项

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