Young Laboratory

The Young lab is mapping the transcriptional regulatory circuitry that controls cell state and differentiation in mice and humans. We use experimental and computational technologies to determine how transcriptional regulators and chromatin modifying enzymes control gene expression programs in embryonic stem cells and differentiated cells.

Professor Young's laboratory has developed powerful genomics methods to map how protein regulators control gene expression programs in healthy and diseased cells. These methods were first used in yeast to discover how gene expression programs are controlled by transcription factors, and signaling pathways. Among the key concepts that emerged from these studies is that transcription factors that control cell state typically regulate their own gene expression, that chromatin modifications span active genes in a spatially specific manner, and that signaling pathways have terminal kinases that generally occupy the set of genes they regulate.

These concepts and genome-wide methods have been used recently to map the transcriptional regulatory networks that control pluripotency and self-renewal in human embryonic stem cells, to determine how epigenetic regulators contribute to the embryonic cell state, and to reveal initiation and elongation control mechanisms in mammalian cells. We discovered that ES cell master transcription factors form an interconnected autoregulatory loop and thus feedback regulate their own expression, that Polycomb and SetDB1 chromatin regulators contribute to silencing of genes encoding developmental regulators, and that certain transcription factors regulate transcription initiation while others regulate elongation.

These studies form the foundation for improved understanding of cellular regulation in human health and disease, for efforts to reprogram cells for regenerative medicine and for development of new therapies for cancer.