Oral Presentation 39th Annual Lorne Genome Conference 2018

Principles of epigenetics and chromatin in development and human disease (#2)

Ali Shilatifard 1
  1. Feinberg School of Medicine, Northwestern University, Chicago, IL, United States

Epigenetic regulation of gene expression in metazoans is central for establishing cellular diversity, and the perturbation of this process results in pathological conditions. Although transcription factors are essential for implementing gene expression programs, they do not function in isolation and require the recruitment of various chromatin-modifying and remodeling machineries. A classic example of developmental gene expression through chromatin is the regulation of the balanced activities of the Polycomb group (PcG) proteins within the PRC1 and PRC2 complexes, and the Trithorax group (TrxG) proteins within the COMPASS family. Recent large scale genome sequencing efforts of human cancer have demonstrated that PcG and COMPASS subunits are highly mutated in a large number of human solid tumors and hematological malignancies. I will discuss our laboratory’s latest biochemical and genetic studies defining the molecular properties of COMPASS and PcG families in the regulation of gene expression, during development, the central role they play in cancer pathogenesis, and how we have taken advantage of such basic molecular information to develop targeted therapeutics for the treatment of hematological malignancies, pediatric brain cancer, and other forms of solid tumors.