发育和物种差异性全球蛋白切换是由BCL11AA驱动的
Vijay G Sankaran1, Jian Xu, Tobias Ragoczy
1Division of Hematology/Oncology, Children's Hospital Boston and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|August 7, 2009
概括
转基因作用因子,如BCL11A,在进化过程中驱动特定物种的基因表达变化. BCL11A表达的差异解释了为什么人类胎儿血红蛋白基因在小鼠中作为胚胎基因起作用.
科学领域:
- 发育生物学 发展生物学
- 进化遗传学 进化遗传学
- 分子生物学分子生物学
背景情况:
- 了解物种间的基因表达差异需要研究 cis 调节元件和跨作用因子.
- 哺乳动物β-环球因子位是发育基因调节的关键模型.
- 转基因小鼠与人类β-环球蛋白位模拟人类胎儿到成人血红蛋白切换.
研究的目的:
- 研究跨作用因子在物种差异性基因调节中的作用.
- 确定小鼠模型对人类环球蛋白切换的局限性.
- 确定调解基因表达进化变化的关键因素.
主要方法:
- 利用携带人类β-环球蛋白位点的转基因小鼠.
- 人类和小鼠系统之间的基因表达模式的比较.
- 分析了BCL11A作为玛环球蛋白表达抑制剂的作用.
主要成果:
- 在小鼠中的人类马环球蛋白 (HBG) 基因模仿了小鼠胚胎环球蛋白基因行为.
- 在老鼠和人类之间,BCL11A的表达有显著差异.
- 缺少BCL11A可以防止小鼠胚胎和人类马球蛋白基因的发育沉默.
结论:
- BCL11A是物种差异性全球蛋白切换的关键媒介.
- 改变的转基因作用因子表达是进化基因表达变化的主要驱动因素.
- 鼠标模型在完全回顾人类发育基因调节方面存在局限性.
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