期刊
MOLECULAR ENDOCRINOLOGY
卷 23, 期 10, 页码 1544-1555出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/me.2009-0045
关键词
-
资金
- European Union [LSHM-CT2005-018652]
The majority of the biological effects of estrogens in the reproductive tract are mediated by estrogen receptor (ER)alpha, which regulates transcription by several mechanisms. Because the tissue-specific effects of some ER alpha ligands may be caused by tissue-specific transcriptional mechanisms of ER alpha, we aimed to identify the contribution of DNA recognition to these mechanisms in two clinically important target organs, namely uterus and liver. We used a genetic mouse model that dissects DNA binding-dependent vs. independent transcriptional regulation elicited by ER alpha. The EAAE mutant harbors amino acid exchanges at four positions of the DNA-binding domain (DBD) of ER alpha. This construct was knocked in the ER alpha gene locus to produce ER alpha((EAAE/ EAAE)) mice devoid of a functional ER alpha DBD. The phenotype of the ER alpha((EAAE/EAAE)) mice resembles the general loss-of-function phenotype of alpha ER knockout mutant mice with hypoplastic uteri, hemorrhagic ovaries, and impaired mammary gland development. In agreement with this phenotype, the expression pattern of the ER alpha((EAAE/EAAE)) mutant mice in liver obtained by genome-wide gene expression profiling supports the observation of a near-complete loss of estrogen-dependent gene regulation in comparison with the wild type. Further gene expression analyses to validate the results of the microarray data were performed by quantitative RT-PCR. The analyses indicate that both gene activation and repression by estrogen-bound ER alpha rely on an intact DBD in vivo. (Molecular Endocrinology 23: 1544-1555, 2009)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据