Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

Chen-Lin Hsieh; Teng Fei; Yiwen ChenTiantian LiYanfei GaoXiaodong WangTong SunChristopher J. SweeneyGwo-Shu Mary LeeShaoyong ChenSteven P. BalkXiaole Shirley LiuMyles BrownPhilip W. Kantoff

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Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

机译：Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

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The androgen receptor (AR) is a key factor that regulates the behavior and fate of prostate cancer cells. The AR-regulated network is activated when AR binds enhancer elements and modulates specific enhancer-promoter looping. Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a wellknown AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e. Here, we demonstrate that KLK3e facilitates the spatial interaction of the KLK3 enhancer and the KLK2 promoter and enhances long-distance KLK2 transcriptional activation. KLK3e carries the core enhancer element derived from the androgen response element III (ARE III), which is required for the interaction of AR and Mediator 1 (Med1). Furthermore, we show that KLK3e processes RNA-dependent enhancer activity depending on the integrity of core enhancer elements. The transcription of KLK3e was detectable and its expression is significantly correlated with KLK3 (R~2 = 0.6213, P < 5 × 10~(-11)) and KLK2 (R~2 = 0.5893, P < 5 × 10~(-10)) in human prostate tissues. Interestingly, RNAi silencing of KLK3e resulted in a modest negative effect on prostate cancer cell proliferation. Accordingly, we report that an androgen- induced eRNA scaffolds the AR-associated protein complex that modulates chromosomal architecture and selectively enhances AR-dependent gene expression.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第20期|7319-7324|共6页
作者
Chen-Lin Hsieh; Teng Fei; Yiwen ChenTiantian LiYanfei GaoXiaodong WangTong SunChristopher J. SweeneyGwo-Shu Mary LeeShaoyong ChenSteven P. BalkXiaole Shirley LiuMyles BrownPhilip W. Kantoff;
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作者单位

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115;

Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
KLK3e/AR/Med1 complex; chromosomal looping;

Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

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