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BBB seminar: Marit Bakke

Epigenetic control of a cell-specific transcription factor

Marit Bakke
Department of Biomedicine, University of Bergen

Steroidogenic factor 1 (SF-1) is expressed in a time and cell-specific manner in the endocrine system. The transcriptional regulation of the gene encoding this transcription factor is complex and is controlled both by a proximal promoter and intronic enhancers, as well as epigenetic mechanisms. We recently identified a region within the SF-1 gene that epigenetically directs cell specific expression through methylation of CpG. DNA methylation analyses revealed a nearly perfect correlation between the methylation status of the proximal promoter and protein expression, such that it was hypomethylated in cells that express SF-1, but hypermethylated in nonexpressing cells. Moreover, in vitro methylation of this region completely repressed reporter gene activity in transfected steroidogenic cells. Bisulfite sequencing of DNA from embryonic tissue demonstrated that the proximal promoter was unmethylated in the developing testis and ovary, whereas it was hypermethylated in tissues that do not express SF-1. Together these results indicate that the DNA methylation pattern is established early in the embryo and stably inherited thereafter throughout development to confine SF-1 expression to the appropriate tissues. These results will be discussed at the seminar together with ongoing experiments designed to reveal the mechanisms that directs methylation and transcriptional control of the SF-1 gene.

Chair: Stein Ove Døskeland <stein.doskeland@biomed.uib.no>, Department of Biomedicine