定义CREB规则:对转录因子监管区域的全基因组分析
Soren Impey1, Sean R McCorkle, Hyunjoo Cha-Molstad
1Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA. impeys@ohsu.edu
Cell
|December 29, 2004
概括
研究人员使用一种称为染色质占用量序列分析 (SACO) 的新方法确定了CREB转录因子的新目标. 这为CREB结合部位提供了一个全面的地图,这对于理解细胞功能至关重要.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 神经科学是一个神经科学.
背景情况:
- CREB转录因子在调节关键细胞过程中发挥着至关重要的作用,如分化,生存和突触可塑性.
- 然而,负责调解这些多样化的细胞反应的完整的CREB目标仍然在很大程度上未被描述.
研究的目的:
- 开发和实施一种用于全面识别CREB目标基因的新方法.
- 定义CREB结合位点的基因组景观及其与注释基因和调控元素的关联.
主要方法:
- 开发染色体占用量序列分析 (SACO),一种将染色体免疫沉 (ChIP) 与修改的SAGE (基因表达序列分析) 方法相结合的技术.
- 将SACO应用于大鼠PC12细胞,以生成基因组签名标签 (GST) 的库.
- 对GST进行生物信息分析,以确定独特的基因组位点并确认CREB结合.
主要成果:
- 识别了大约41,000个基因组签名标签 (GSTs),将它们映射到独特的基因组位置.
- 确认CREB在多个GST支持的位点上具有约束性,确定了6302个位点.
- 鉴定的基因与注释基因 (40%),CpG岛屿 (49%) 和假定的cAMP响应元素 (CREs) (72%) 的显著重叠.
- 发现了许多双向促进器和与CREB结合部位相关的新型反意义转录.
结论:
- SACO方法提供了一种强大而全面的方法,用于全基因组映射转录因子结合位.
- 这项研究提供了迄今为止对甲动物物种转录因子结合位点的最广泛的定义.
- 这些发现为CREB管理的监管网络提供了关键的见解,影响了我们对细胞分化,生存和可塑性的理解.
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