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Publication : Research resource: Aorta- and liver-specific ERα-binding patterns and gene regulation by estrogen.

First Author  Gordon FK Year  2014
Journal  Mol Endocrinol Volume  28
Issue  8 Pages  1337-51
PubMed ID  24992180 Mgi Jnum  J:216234
Mgi Id  MGI:5608541 Doi  10.1210/me.2013-1395
Citation  Gordon FK, et al. (2014) Research resource: Aorta- and liver-specific ERalpha-binding patterns and gene regulation by estrogen. Mol Endocrinol 28(8):1337-51
abstractText  Estrogen has vascular protective effects in premenopausal women and in women younger than 60 years who are receiving hormone replacement therapy. However, estrogen also increases the risks of breast and uterine cancers and of venous thromboses linked to up-regulation of coagulation factors in the liver. In mouse models, the vasculoprotective effects of estrogen are mediated by the estrogen receptor alpha (ERalpha) transcription factor. Here, through next-generation sequencing approaches, we show that almost all of the genes regulated by 17beta-estradiol (E2) differ between mouse aorta and mouse liver, ex vivo, and that this difference is associated with a distinct genomewide distribution of ERalpha on chromatin. Bioinformatic analysis of E2-regulated promoters and ERalpha binding site sequences identify several transcription factors that may determine the tissue specificity of ERalpha binding and E2-regulated genes, including the enrichment of NF-kappaB, AML1, and AP1 sites in the promoters of E2 down-regulated inflammatory genes in aorta but not liver. The possible vascular-specific functions of these factors suggest ways in which the protective effects of estrogen could be promoted in the vasculature without incurring negative effects in other tissues.
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