Myometrial transcriptional regulation of the gap junction gene, connexin-43

Reproduction, Fertility, and Development
D L LefebvreS J Lye

Abstract

The mechanisms that enable the myometrium to switch from a state of relative quiescence during pregnancy to a muscle that is spontaneously active, very responsive to endogenous uterotonins and exhibits a high degree of cell-cell coordination are poorly understood. It is hypothesized that this switch or 'activation' of the myometrium results from the coordinated expression of a cassette of 'contraction-associated proteins'. The molecular mechanisms that regulate the expression of one of these, namely the myometrial gap junction protein connexin-43 (Cx-43), have been analysed. Myometrial Cx-43 expression is significantly increased during labour, associated with an increase in plasma oestrogen:progesterone, and positively regulated by oestrogen in non-pregnant rats. The genomic structure of the murine Cx-43 gene and the sequence of its 5' flanking sequence are reported here. This region functions as a promoter and contains several putative cis-acting elements which may be important in the regulation of Cx-43 transcription. Among these elements are several half-palindromic sequences that may function as oestrogen response elements and several AP-1 sites that may bind the transcription factors Fos and Jun. Oestrogen treatment of cel...Continue Reading

Citations

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