Project 464581

During development, genes have to be activated and silenced at precise times and places in order for an embryo to make all of the right tissues and survive. This is done in part by DNA methylation, which is a chemical modification of DNA critical for "silencing" genes. DNA methylation is also responsible for silencing transposons. These parasitic DNA elements act like viruses, except that they make copies of themselves and multiply within the genome itself. Transposons can cause dangerous mutations within the cell if not kept in check. For an embryo to develop properly, DNA methylation from the previous generation must be removed and replaced, which puts the embryo in "danger" and therefore requires sophisticated mechanisms of gene and transposon silencing. We discovered that a gene called ZMYM2 is important for promoting the DNA methylation of key genes and transposons. Mice lacking ZMYM2 die early in development, expressing the wrong genes and showing explosive upregulation of transposons. More specifically, transposons as well as genes that should be expressed only during gamete formation (spermatogenesis) start to be expressed throughout the embryo. Our goal is to understand how the ZMYM2 gene works to prevent this dangerous outcome and allow healthy development.