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 cells transiently transfected with a plasmid containing the Cx-43 promoter linked to the chloramphenicol acetyl transferase (CAT) gene, increased CAT activity indicating that the murine Cx-43 gene is oestrogen responsive. In addition, treatment of rats with oestrogen significantly increased mRNA encoding c-fos and c-jun in the myometrium and this occurred before any increase in Cx-43 mRNA. These data suggest that oestrogen may increase transcription of the Cx-43 gene through direct mechanisms (via the putative oestrogen response elements) or indirect mechanisms (by increased expression of c-fos and c-jun acting via the putative AP-1 sites). Since oestrogen may be an important modulator of myometrial activation, these mechanisms may be critical to the processes leading to increased synthesis of gap junctions at term and, hence, to the onset of labour.

Overall, methylation of the p16INK4a gene promoter is found in psoriatic epidermis, which is associated with the mRNA level of p16INK4a expression and activity of the disease. These data indicate that methylation of the p16INK4a promoter may play a potential role in the pathogenesis of psoriasis.

Effective comparative mapping inference utilizing developing gene maps of animal species requires the inclusion of anchored reference loci that are homologous to genes mapped in the more "gene-dense" mouse and human maps. Nominated anchor loci, termed comparative anchor tagged sequences (CATS), have been ordered in the mouse linkage map, but due to the dearth of common polymorphisms among human coding genes have not been well represented in human linkage maps. We present here an ordered framework map of 314 comparative anchor markers in humans based on mapping analysis in the Genebridge 4 panel of radiation hybrid cell lines, plus empirically optimized CATS PCR primers which detect these markers. The ordering of these homologous gene markers in human and mouse maps provides a framework for comparative gene mapping of representative mammalian species.