SEXUALLY DIMORPHIC DNA DEMETHYLATION IN THE PROMOTER OF THE SLP (SEX-LIMITED PROTEIN) GENE IN MOUSE-LIVER

Mouse Slp, a duplicate of the fourth complement component (C4) gene, e xhibits EDTA-independent complement activity with a hepatic expression that is male specific. To provide an underlying mechanism for the mal e-specific expression, we have analyzed the promoter activity of the v arious 5'-flanking sequences and CpG demethylation of the Slp gene. Tr ansient transfections using HepG2 cells indicate that the element TTCC GGGC (nt -124 to -117) regulates the promoter activity. Moreover, CpG at position -121 of this regulatory element is demethylated to a much higher degree in males than in females. This sexually dimorphic DNA de methylation is consistent with the male-specific expression of the Slp gene in DBA/2 males. The regulatory element binds to the different TT CCGGGC-specific nuclear proteins depending on the methylation of the C pG site. In contrast, the corresponding CpG at position -119 of the C4 gene, which is expressed in both males and females, is demethylated a t equal and high levels in both sexes. We therefore propose that the D NA demethylation and methylation-sensitive transcription factors may b e a part of the regulatory mechanism for the male-specific expression of the Slp gene.