| First Author | Ahlbory-Dieker DL | Year | 2009 |
| Journal | Mol Endocrinol | Volume | 23 |
| Issue | 10 | Pages | 1544-55 |
| PubMed ID | 19574448 | Mgi Jnum | J:152849 |
| Mgi Id | MGI:4360138 | Doi | 10.1210/me.2009-0045 |
| Citation | Ahlbory-Dieker DL, et al. (2009) DNA binding by estrogen receptor-alpha is essential for the transcriptional response to estrogen in the liver and the uterus. Mol Endocrinol 23(10):1544-55 |
| abstractText | 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 ERalpha ligands may be caused by tissue-specific transcriptional mechanisms of ERalpha, 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 ERalpha. The EAAE mutant harbors amino acid exchanges at four positions of the DNA-binding domain (DBD) of ERalpha. This construct was knocked in the ERalpha gene locus to produce ERalpha((EAAE/EAAE)) mice devoid of a functional ERalpha DBD. The phenotype of the ERalpha((EAAE/EAAE)) mice resembles the general loss-of-function phenotype of alphaER knockout mutant mice with hypoplastic uteri, hemorrhagic ovaries, and impaired mammary gland development. In agreement with this phenotype, the expression pattern of the ERalpha((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 ERalpha rely on an intact DBD in vivo. |
