• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >DNase I-hypersensitive sites I and II of the human growth hormone locus control region are a major developmental activator of somatotrope gene expression
【2h】

DNase I-hypersensitive sites I and II of the human growth hormone locus control region are a major developmental activator of somatotrope gene expression

机译：人类生长激素基因座控制区的DNase I超敏感位点I和II是生长激素基因表达的主要发育激活因子

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

High-level expression of the human growth hormone (hGH) gene is limited to somatotrope and lactosomatotrope cells of the anterior pituitary. We previously identified a locus control region (LCR) for the hGH gene composed of four tissue-specific DNase I-hypersensitive sites (HS) located between −14.6 kb and −32 kb 5′ to the hGH transcription start site that is responsible for establishing a physiologically regulated chromatin domain for hGH transgene expression in mouse pituitary. In the present study we demonstrated that the LCR mediates somatotrope and lactosomatotrope restriction on an otherwise weakly and diffusely expressed hGH transgene. The subregion of the LCR containing the two pituitary-specific HS, HSI and HSII (−14.6 to −16.2 kb relative to the hGH promoter and denoted HSI,II), was found to be sufficient for mediating somatotrope and lactosomatotrope restriction, for appropriately timed induction of hGH transgene expression between embryonic days 15.5 and 16.5, and for selective extinction of hGH expression in mature lactotropes. When studied by cell transfection, the HSI,II fragment selectively enhanced transcription in a presomatotrope-derived cell line, although at levels (2- to 3-fold) well below that seen in vivo. The LCR activity of the HSI,II element was therefore localized by scoring transgene expression in fetal founder pituitaries at embryonic day 18.5. The data from these studies indicated that a 404-bp segment of the HSI,II region encodes a critical subset of LCR functions, including the establishment of a productive chromatin environment, cell-specific restriction and enhancement of expression, and appropriately timed induction of the hGH transgene during embryonic development.
机译：人类生长激素（hGH）基因的高水平表达仅限于垂体前叶的体细胞和泌乳体细胞。我们之前已经确定了hGH基因的基因座控制区（LCR），该基因由四个组织特异性DNase I超敏感位点（HS）组成，位于-14.6 kb和-32 kb之间，距离hGH转录起始位点5'小鼠垂体中hGH转基因表达的生理调节染色质结构域。在当前的研究中，我们证明了LCR介导了生长激素和乳糖生长激素对其他表达弱的hGH转基因的限制。 LCR的包含两个垂体特异性HS，HSI和HSII（相对于hGH启动子为-14.6至-16.2 kb，表示为HSI，II）的子区域已被发现足以介导生长激素和乳杆菌营养限制，并在适当的时间进行hGH转基因表达在胚胎第15.5天至16.5天之间的诱导，并在成熟的嗜乳酸菌中选择性消灭hGH表达。当通过细胞转染研究时，HSI，II片段选择性地增强了源自拟真变种的细胞系中的转录，尽管其水平（2-3倍）远低于体内观察到的水平。因此，HSI，II元件的LCR活性通过在胚胎第18.5天在胎儿创立者垂体中对转基因表达进行评分来定位。这些研究的数据表明，HSI，II区的404 bp片段编码LCR功能的关键子集，包括建立高效的染色质环境，细胞特异性的限制和表达增强，以及适当的时间诱导。胚胎发育过程中的hGH转基因。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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