对雌激素受体结合的全染色体映射揭示了需要分叉蛋白FoxA1的长距离调节
Jason S Carroll1, X Shirley Liu, Alexander S Brodsky
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
在人类染色体上绘制了雌激素受体 (ER) 结合位. 直接ER结合需要叉头因子FoxA1,它对于乳腺癌中雌激素诱导的基因表达至关重要.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 雌激素在生殖和乳腺癌中至关重要.
- 了解基因的 cis 调节元件是有限的.
- 雌激素受体 (ER) 功能是乳腺癌的关键.
研究的目的:
- 在人类21号和22号染色体上绘制ER结合点的地图.
- 调查 cis 监管元素的组织.
- 确定ER染色体协会和基因调节所必需的因素.
主要方法:
- 染色体免疫沉 (ChIP) 与状微阵列相结合.
- 对ER关联的全基因组映射.
- 在FoxA1被淘汰后进行基因表达分析.
主要成果:
- ER选择性地结合到特定的部位,通常远离基因起始部位.
- 直接ER结合需要靠近叉头因子结合点.
- FoxA1 knockdown 抑制ER染色体结合和雌激素诱导的基因表达.
结论:
- FoxA1对于调解乳腺癌细胞中的雌激素反应至关重要.
- ER与染色质的结合受其他转录因子的调节.
- 这项研究提供了对ER功能基因组组织的见解.
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