Aberrant chromatin regulation is a hallmark of multiple developmental diseases including cancer. Various chromatin marks such as DNA methylation and histone modifications, known as “epigenetic marks”, are implicated in the dynamic regulation of chromatin structure and lineage specific gene expression. Epigenetic regulators are recurrently mutated in cancer. The reversible nature of epigenetic marks holds great therapeutic promise. Therefore much effort is devoted to developing small molecule epigenetic inhibitors however such approaches are targeting the entire genome, causing multiple unintended side effects. I am proposing to develop tools that enable locus-specific manipulation of chromatin structure and function. Bu using such locus specific epigenetic engineering tools, I aim to alter aberrantly regulated local epigenetic modifications at specifically targeted genomic region.