Mol. Hum. Reprod. Advance Access published online on August 3, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gal067
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1 Department of Obstetrics and Gynecology; Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, TX, USA
* To whom correspondence should be addressed. The myometrial oxytocin receptor (OTR) is highly regulated during pregnancy, reaching maximal concentrations near term. These levels are then abruptly reduced in advanced labour and the post-partum period. Our goal was to examine the molecular basis for this reduction, using chromatin immunoprecipitation (ChIP). Interleukin-1
Received May 25, 2006
Revised June 23, 2006
Accepted June 29, 2006
Article
Interleukin-1-induced NF-
Melvyn S. Soloff 1 *, Michael G. Izban 2 *, Dennis L. Cook Jr 2, Yow-Jiun Jeng 2, and Randy C. Mifflin 3
B recruitment to the oxytocin receptor gene inhibits RNA polymerase II-promoter interactions in cultured human myometrial cells
2 Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA
3 Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
Melvyn S. Soloff, E-mail: msoloff{at}utmb.edu
Abstract 
(IL1A) treatment of cultured human myo-metrial cells has previously been shown to reduce steady-state levels of OTR mRNA. We show further that IL1A reduced RNA polymerase II cross-linking to the otr promoter, as reflective of transcriptional inhibition. IL1A also increased the recruitment of nuclear factor 
B (NF-B) to a site 955 bp upstream from the transcriptional start site. Inhibition of NF-B activation negated the effects of IL1A on polymerase II dissociation, indicating a causal relationship, at least in part, between recruitment of NF-B and detachment of polymerase from the otherwise constitutively active otr promoter. IL1A treatment also resulted in increased his-tone H4 acetylation in the otr promoter region. Whereas NF-B recruitment and histone acetylation are generally associated with activation of gene expression, our findings show that both processes can be involved in dissociation of RNA polymerase II from an active promoter. The results of these studies suggest that the elevation of IL1 in the myometrium occurring at the end of pregnancy initiates the process of down-regulation of OTRs in advanced labour, resulting in the desensitization of the myometrium to elevated levels of OT in the blood during lactation.B/oxytocin receptor.
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