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Articles by S. C Hewitt
Total Records ( 1 ) for S. C Hewitt
  S. C Hewitt , J. E O'Brien , J. L Jameson , G. E Kissling and K. S. Korach

In vitro models have been used to demonstrate that estrogen receptors (ERs) can regulate estrogen-responsive genes either by directly interacting with estrogen-responsive element (ERE) DNA motifs or by interacting with other transcription factors such as AP1. In this study, we evaluated estrogen (E2)-dependent uterine gene profiles by microarray in the KIKO mouse, an in vivo knock-in mouse model that lacks the DNA-binding function of ER and is consequently restricted to non-ERE-mediated responses. The 2- or 24-h E2-mediated uterine gene responses were distinct in wild-type (WT), KIKO, and ERKO genotypes, indicating that unique sets of genes are regulated by ERE and non-ERE pathways. After 2 h E2 treatment, 38% of the WT transcripts were also regulated in the KIKO, demonstrating that the tethered mechanism does operate in this in vivo model. Surprisingly, 1438 E2-regulated transcripts were unique in the KIKO mouse and were not seen in either WT or ERKO. Pathway analyses revealed that some canonical pathways, such as the Jak/Stat pathway, were affected in a similar manner by E2 in WT and KIKO. In other cases, however, the WT and KIKO differed. One example is the Wnt/β-catenin pathway; this pathway was impacted, but different members of the pathway were regulated by E2 or were regulated in a different manner, consistent with differences in biological responses. In summary, this study provides a comprehensive analysis of uterine genes regulated by E2 via ERE and non-ERE pathways.

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