Abstract: Series 113, Lecture 6

The Harvey Lectures Series 113 (2017—2018)

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Lecture #6: Thursday, April 19, 2018 — Time and Location

Varying the Terrain of Epigenetic Landscapes: Implications for Gene Regulation, Development and Cancer

C David Allis, PhD

C David Allis, PhD

Joy and Jack Fishman Professor and Head of the Laboratory of Chromatin Biology and Epigenetics

The Rockefeller University

New York, New York

Dr Allis's Website

Although every gene exists within every cell in the human body, only a small percentage of genes are activated in any given cell or tissue type. In eukaryotes, nature has evolved a sophisticated indexing system that facilitates access to specific genes when needed. This system relies on a DNA-histone protein complex called chromatin to efficiently package the genetic information that exists within each cell type, giving rise to ‘epigenomes’. This packaging system makes certain expressed genes, or genes to be expressed, are more readily accessible to transcription factors and other machinery that must engage our genetic template. Our laboratory is perhaps best known for deciphering regulatory mechanisms that impinge upon chromatin and for identifying the responsible enzyme systems that govern the covalent modifications of histone proteins. The regulation of the enzyme systems responsible for adding or subtracting modifications from histones and DNA, or for reading them, are taking center stage in the study of cancer in the current post-genomic or epigenomic era.

Recent studies are centered upon histone mutations (‘oncohistones’), representing a previously unrecognized mechanism to alter epigenetic states in a variety of pathologies through inhibition of a wide range of histone methyltransferases. In turn, oncohistone mutations exert their oncogenic effect by reprogramming the cellular epigenome and transcriptome, thereby disrupting the highly coordinated epigenetic programs required for cell-specific differentiation. Implications of this research for human biology and human disease, notably cancer, are far-reaching and continuing at a remarkable pace.