Estrogen Regulation of Gene Expression and Analysis of the Role of the Coregulator, Repressor of Estrogen Receptor Activity (Rea)

To elucidate the functional activities of REA in diverse estrogen target tissues in vivo, I have used targeted disruption to ablate the REA gene in mice. Genotyping revealed that homozygous animals are not viable, suggesting a crucial role for REA in early development. The viability of heterozygous animals is similar to that of wild type, and female heterozygous animals have an increased body weight relative to age-matched wild-type animals beginning after puberty. Studies in immature heterozygous animals revealed a greater uterine weight gain in response to estradiol (E2) and a greater stimulation of E2 up-regulated genes and a loss of down regulation in genes normally suppressed by E2 in the uterus. Analysis of the histology of the uterus and mammary gland in REA wild type and heterozygous mice revealed gene dosage developmental effects of REA and changes in E2-responsiveness. Studies using mouse embryo fibroblasts (MEFs) revealed that REA heterozygous MEFs displayed a greater transcriptional response to E2. These studies demonstrate that REA is a significant modulator of estrogen responsiveness in vivo.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Molecular and Integrative Physiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Park, Seongeun

Contributors dc:contributor

• Katzenellenbogen, Benita S.

• Biology, Molecular

Language dc:language

eng

Identifier

(MiAaPQ)AAI3131003

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/87229