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Lookup NU author(s): Dr Magdalena Karolczak-Bayatti, Tamer Abu-Amara, Emeritus Professor Nick Europe-Finner
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In this study, we show that myometrial transcriptional complexes consisting of Sp1, Sp3, histone deacetylase (HDAC)1/2, RbAp48, and mSin3A are recruited to 4 out of the 6 Sp1-4 sites within the Gαs promoter. Moreover disruption in the binding of these complexes via mithramycin administration results in a substantial decrease in expression of Gαs proteins in myometrial cell cultures. In many instances, these transcriptional regulatory complexes repress expression of genes having a high CG content within their promoter region. This repression can be attenuated by inhibition of HDAC activity by the class I/II HDAC inhibitor trichostatin A (TSA) resulting in increased gene transcription. However, although a substantial increase in Gαs protein levels was observed upon administration of TSA to primary cultures of human myometrial cells, this was not preceded by an increase in messenger RNA (mRNA) and thus an elevation in gene transcription. Importantly the increase in Gαs protein levels occurred via ubiquitination and inhibition of proteasomal activity, indicating that this pathway is also involved in regulating Gαs protein expression during pregnancy and parturition.
Author(s): Karolczak-Bayatti M, Abu-Amara TMM, Europe-Finner GN
Publication type: Article
Publication status: Published
Journal: Reproductive Sciences
Year: 2012
Volume: 19
Issue: 12
Pages: 1323-1331
Print publication date: 08/08/2012
ISSN (print): 1933-7191
ISSN (electronic): 1933-7205
Publisher: Sage Publications, Inc.
URL: http://dx.doi.org/10.1177/1933719112450339
DOI: 10.1177/1933719112450339
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