title: Research resource: Aorta- and liver-specific ERα-binding patterns and gene regulation by estrogen.
abstract: 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 α (ERα) transcription factor. Here, through next-generation sequencing approaches, we show that almost all of the genes regulated by 17β-estradiol (E2) differ between mouse aorta and mouse liver, ex vivo, and that this difference is associated with a distinct genomewide distribution of ERα on chromatin. Bioinformatic analysis of E2-regulated promoters and ERα binding site sequences identify several transcription factors that may determine the tissue specificity of ERα binding and E2-regulated genes, including the enrichment of NF-κB, 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.
authors.affiliation: Molecular Cardiology Research Institute (F.K.G., C.S.V., L.I.K., G.R.S.), Tufts Medical Center, Boston, Massachusetts 02111; and Medical Oncology Department (M.W. M.B.), Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Francesca K
authors.initials: FK
authors.lastname: Gordon
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Vallaster
authors.forename: Thomas
authors.initials: T
authors.lastname: Westerling
authors.forename: Lakshmanan K
authors.initials: LK
authors.lastname: Iyer
authors.forename: Myles
authors.initials: M
authors.lastname: Brown
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Schnitzler
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D016384:Consensus Sequence; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D002843:Chromatin; D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol