The transcriptional response of mouse uterus to estrogen is genetically regulated
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ABSTRACT: The growth and development of the uterus in response to 17β-estradiol (E2) is genetically controlled, with marked variation observed depending on the mouse strain studied. Previous work from our laboratory using inbred mice that are high (C57BL6/J; B6) or low (C3H/HeJ; C3H) responders to E2 has led to the identification of quantitative trait loci (QTL) associated with phenotypic variation in uterine growth and eosinophil infiltration. The mechanisms underlying differential responsiveness to E2, and the genes involved, are unknown. Therefore, we used a microarray approach to show association of distinct E2-regulated transcriptional signatures with genetically controlled high and low responses to E2. Among the 6,664 E2-responsive uterine transcripts, several reside within our previously identified QTL, including the ERα-tethering factor Runx1, demonstrated to enhance E2-mediated transcript regulation. The level of RUNX1 in uterine epithelial cells was shown to be 3.5-fold greater in B6 compared to C3H. Analysis of cellular functions in sets of strain-dependent E2-responsive transcripts indicated C3H-selective enrichment of apoptosis, consistent with a 7-fold increase in the apoptosis indicator CASP3, and a 2.4-fold decrease in the apoptosis inhibitor Naip1 in C3H vs. B6 following treatment with E2. Our novel insights into the mechanisms underlying the genetic control of tissue sensitivity to estrogen have great potential to advance understanding of individualized effects in physiological and disease states.
ORGANISM(S): Mus musculus
PROVIDER: GSE38800 | GEO | 2013/06/11
SECONDARY ACCESSION(S): PRJNA168642
REPOSITORIES: GEO
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