How is epigenetic variation established?

Epigenetic processes are fundamental to the differentiation and development of multicellular organisms by controlling chromatin accessibility and transcription. Although phenotypic variation is mainly driven by genetic traits, there is evidence that epigenetic mechanisms may contribute to inter-individual phenotypic differences in mammals. But the exact processes leading to inter-individual epigenetic differences are often unclear. Besides being triggered by environmental influences, epigenetic differences between individuals may also be inherited; however, the relationship between epigenetic traits and inter-individual genetic differences is often unclear.

By comparing two inbred mouse strains, we could previously show that strain-specific DNA methylation events are mainly determined by cis-acting sequences, but to some extent also in trans, indicating the presence of strain-specific epigenetic modifier genes. Ongoing work in the lab uses inbred mouse strain comparisons to identify factors responsible for the epigenetic programming in cis and in trans during development. This work will reveal fundamental insights into the inheritance and establishment of individual DNA methylation patterns.