在人类21号和22号染色体沿线对转录因子结合位点的无偏向地绘制地图,有助于广泛调节非编码RNAs
Simon Cawley1, Stefan Bekiranov, Huck H Ng
1Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA.
Cell
|February 26, 2004
概括
这项研究绘制了人类基因组中的转录因子结合部位 (TFBS),揭示了Sp1,cMyc和p53.3的数千个部位. 许多TFBS调节非编码RNA,这表明协调基因调节.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 了解转录因子结合对于破译基因调节至关重要.
- 以前用于映射转录因子结合位点 (TFBS) 的方法在范围和公正性上是有限的.
- 越来越多地认识到非编码RNA的作用及其由转录因子调节的作用.
研究的目的:
- 为了在人体染色体21和22上的Sp1,cMyc和p53转录因子的体内结合部位进行公正的映射.
- 估计这些关键因素的全基因组分布和TFBS数量.
- 研究TFBS,蛋白质编码基因和非编码RNA之间的关系.
主要方法:
- 利用高密度的寡核酸阵列,覆盖人类染色体21和22的非重复序列.
- 在体内测绘DNA结合转录因子 (Sp1,cMyc,p53) 的结合位点.
- 推断结果以估计全基因组TFBS数量,并分析它们相对于基因和非编码RNA的基因位置.
主要成果:
- 确定了大量的TFBS,外推估计Sp1至少有12,000个,cMyc有25,000个,p53有1600个.
- 发现只有22%的TFBS位于蛋白质编码基因的5'端;36%位于基因内或下游,与非编码RNA相关联.
- 观察到非编码RNA调节 (例如,通过视网酸) 和重叠的蛋白质编码和非编码RNA合调之间存在显著的相关性.
结论:
- 人类基因组拥有大量的TFBS,显著影响蛋白质编码和非编码基因表达.
- 很大一部分TFBS与非编码RNA相关,突出显示了它们的监管重要性.
- 共同的转录因子和环境信号可能协调蛋白质编码和非编码基因的调节,这表明一个复杂的调节网络.
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