Epigenetic modifications to DNA play a crucial role in the determination of the phenotype of an organism by
controlling patterns of gene expression. Cytosine methylation and repressive histone modifications are examples of
epigenetic modifications that are associated with genes that are transcriptionally inert, while active histone
modifications are associated with transcriptional activity.
Little is currently known about the rules that determine which parts of the genome acquire which type of
modifications. We do know that the different epigenetic states correlate with the locus being active in some cells
and inactive in others resulting in a variegated phenotype. This phenomenon can even extend to the whole
organism resulting in isogenic individuals with different phenotypes. In some cases these epigenetic states can
actually be inherited through meiosis resulting in transgenerational effects (epigenetic inheritance).
In the proposed project a forward genetic approach is planned to be used to identify and characterize mutations in
genes that are needed for the establishment and maintenance of epigenetic state in the mouse. Epigenetic
phenomena such as variegation, variable expressivity and epigenetic inheritance are not understood at a molecular
level and the identification of genes involved in the establishment and maintenance of epigenetic marks will be a
start to the characterisation of the mechanisms involved.