CCCTC-binding Factor Acts Upstream of FOXA1 and Demarcates the Genomic Response to Estrogen*
CCCTC-binding Factor Acts Upstream of FOXA1 and Demarcates the Genomic Response to Estrogen*
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DOI：
10.1074/jbc.m110.149658
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发表时间：
2010-07
期刊：
影响因子：
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通讯作者：
Yu Zhang;Jing Liang;Yanyan Li;C. Xuan;Feng Wang;Dandan Wang;Lei Shi;Di Zhang;Y. Shang
中科院分区：
文献类型：
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作者：
Yu Zhang;Jing Liang;Yanyan Li;C. Xuan;Feng Wang;Dandan Wang;Lei Shi;Di Zhang;Y. Shang
雌激素受体（ER）的转录激活是快速和动态的。如何建立和维持迅速和精确的ER反应仍然没有完全理解。在这里，我们报告了两个边界元素周围的明确界定的ERα靶TFF1基因座被CCCTC结合因子（CTCF）占据。这些元件相隔40 kb，但聚集在核空间中，这取决于CTCF，但不依赖于雌激素和转录。相反，在雌激素非响应性乳腺癌细胞中，这两个元件的空间接近性丢失，整个基因座反而显示出多梳抑制复合物2控制的异染色质特征。我们发现CTCF在决定对雌激素的基因组反应的“先锋”因子FOXA 1的上游起作用。我们认为CTCF结合的边界元件区分了活性区域和非活性区域，建立了一个邻近染色体区域的框架，该框架倾向于ERα调节转录。
Transcription activation by estrogen receptor (ER) is rapid and dynamic. How the prompt and precise ER response is established and maintained is still not fully understood. Here, we report that two boundary elements surrounding the well defined ERα target TFF1 locus are occupied by the CCCTC-binding factor (CTCF). These elements are separated by 40 kb but cluster in the nuclear space depending on CTCF but independent of estrogen and transcription. In contrast, in estrogen non-responsive breast cancer cells, the spatial proximity of these two elements is lost and the entire locus instead displays a polycomb repressive complex 2-controlled heterochromatin characteristic. We showed that CTCF acts upstream of the “pioneer” factor FOXA1 in determining the genomic response to estrogen. We propose that the CTCF-bound boundary elements demarcate active versus inactive regions, building a framework of adjacent chromosome territory that predisposes ERα-regulated transcription.