9506784 Engler Ssm1(strain-specific modifier) is a locus on distal mouse chromosome 4 that controls the methylation of a class of transgenic targets and presumably endogenous sequences as well. Because any detailed understanding of how Ssm1 functions depends upon cloning the gene, the first goal of this project is to isolate the murine Ssm1 locus using positional cloning techniques. A high resolution genetic map of the involved region will be made in order to specifically locate the locus. Clones from existing libraries will be analyzed in order to identify the region of DNA containing the gene. A second goal is to characterize specific targets of the Ssm1 modifier locus and efforts will begin to isolate endogenous sequences whose methylation might be controlled by Ssm1. A third aim is to identify any other genes which might be required in addition to Ssm1 for methylation of the target genes to occur. %%% The regulation of gene expression in eukaryotic cells is much more complicated than was first believed. It is now known that epigenetic effects such as gene methylation can be the determining factor in gene expression. A gene which controls the methylation of target genes in the mouse will be isolated by positional cloning and analyzed. It is the first such locus to be characterized in mammals and detailed understanding of its mode of action should greatly expand our knowledge of mechanisms of gene silencing in higher organisms. ***
