Mammalian development relies on a complex interplay between genetic and epigenetic factors to create trillions of highly specialized cells from the same genetic blueprint. This process is orchestrated by gene regulatory sequences encoded in DNA, which in turn are influenced by epigenetic properties including DNA methylation, DNA packaging, and modifications of DNA packaging proteins. Mammalian genomes contain hundreds of epigenetic regulators — collectively referred to as the “epigenetic machinery” — which are responsible for reading, writing, and erasing this epigenetic information. Our research seeks to understand how the epigenetic machinery works, and how its malfunction contributes to disease.
Current directions in the lab seek to answer the following key questions about the epigenetic machinery:
1. What are the specific regulatory sequences and target genes influenced by components of the epigenetic machinery, and in what cell types/contexts?
2. How are components of the epigenetic machinery recruited to specific regions of the genome (e.g. regulatory sequences) in specific cellular contexts?
3. By what mechanisms do disease-causing mutations in components of the epigenetic machinery give rise to phenotypes at the molecular, cellular, and organismal levels.
To answer these questions, we use a variety of tools including epigenomics, genome-editing, single-cell genomics, and computational biology, with a focus on mouse developmental and human cell culture models.