William Pastor

Almost every cell type in the human body has the exact same DNA, a complete human genome, and yet each cell type expresses a distinct set of genes which shapes its identity and allows it to perform its function. This ability to express different genes from the same genome is facilitated by epigenetic marks: chemical modifications of DNA and histones. Our lab uses stem cells and model organisms to determine how the epigenome is shaped during human development. Our three main areas of study are: 1. DNA methylation establishment. Methylation of the 5-position of cytosine (DNA methylation) is a critical epigenetic silencing mark. During early human development, almost all DNA methylation is lost and then re-established with specific patterns in different lineages. Our lab studies how DNA methylation is targeted to specific parts of the genome and how it controls transcription in different cell types. 2. Placental development. In the first developmental decision in embryonic development, certain cells are specified as “trophoblasts”. The trophoblasts go on to form most of the placenta, the organ which transports nutrition to the developing embryo and secretes hormones that guide the course of pregnancy. Defects in placental development are detrimental to fetal and maternal health, and remarkably, many types of cancer recapitulate aspects of the placental epigenome. Our lab studies the transcription factors and epigenetic regulators important in trophoblast specification and placental development. 3. The many roles of ZMYM2. We discovered that a transcriptional repressor called ZMYM2 is a critical factor in guiding DNA methylation in early development. We also have evidence that it is a critical transcriptional corepressor in other developmental contexts, and we are presently mapping out how and where this protein acts during mammalian development.