Chromatin Biology and Epigenetics
The Rockefeller University
New York, NY
Allis, C. David
Although every gene exists within every cell in the human body, only a small percentage of genes are activated in any given cell. To manage this genetic information efficiently, nature has evolved a sophisticated system that facilitates access to specific genes. Dr. Allis and his colleagues study the DNA-histone protein complex called "chromatin" that packages the genetic information that exists within each cell and serves as a means of gene regulation that lies outside of the DNA itself (the basis of "epigenetics"; see Allis et al., 2006 for a textbook dedicated to this field).
Dr. Allis and his colleagues favor the general view that distinct patterns of covalent histone modifications form a "histone or epigenetic code" that is then read by effector proteins to bring about distinct downstream events (Strahl and Allis, 2000; Cheung et al., 2000; Jenuwein and Allis, 2001). Since histone proteins are highly conserved through evolution, their post-translational modifications, and the enzyme systems responsible for bringing them about, are also well conserved. Thus, members of the Allis lab are currently investigating different PTMs and their biological roles in a variety of unicellular and multicellular eukaryotic models, ranging from yeast to human. One useful way to summarize much of our work is as follows - What are the relevant "marks" in histone proteins, who "writes" these marks, who "erases" them, and who "reads" the marks. In pursuing these questions, we exploit the biological strengths of many experimental models, a "perk" of working with such a conserved structure as the chromatin polymer. The research performed in the Allis laboratory focuses on how chemical changes to histone proteins affect essentially all DNA-templated processes such as gene expression, DNA replication and repair. Through such enzymatic processes as acetylation, methylation, phosphorylation or ubiquitylation, histones are believed to function like a master "on/off switches", determining whether particular genes are active or inactive, and how these states are maintained and propagated in developmental contexts. Knowing how to control which genes to turn on or off, using targeted therapies, could reduce the risk of certain diseases by activating genes that suppress tumor growth and deactivating genes that support it. The implications of this research for human diseases, notably cancer, are now clear (see below).