V AROUND THE INSTITUTE
Epigenetics
TONY RINALDO
EPIGENETICS aims to explain how one genome can give rise to many different ff cellular identities, including muscle cells and neurons.
by Courtney Humphries The cells in our bodies carry the same genome, yet they express information in radically different ff ways. How is it that the same genes produce a hefty, fibrous fi muscle cell and a delicately branching neuron? On February 22, the day that Harvard celebrated the 10th anniversary of mapping the human genome, a Dean’s Lecture at the Radcliff ffe Institute addressed this fundamental question, which the genetic code alone can’t answer. In a talk titled “Beyond the Double Helix: Varying the ‘Histone Code,’” C. David Allis, the Joy and Jack Fishman Professor at Rockefeller University, said a central puzzle of biology is that “one genome has to give rise to many cellular identities.” The problem has led to one of biology’s youngest and most exciting fi fields, epigenetics. The field focuses on the
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way that DNA is physically packaged, wound up with proteins called histones into a complex called chromatin. The structure of chromatin in a given cell determines which genes are transformed into proteins and which lie dormant. Furthermore, “there’s some incredible way to inherit this,” Allis said. When a cell divides, its identity is passed along to its daughter cells by preserving its pattern of gene expression. Allis’s work has focused on small chemical modifi fications to specifi fic areas of histones— which, he and other scientists have proposed, serve as a kind of “histone code” determining which genes are expressed and which are silenced. Scientists are now uncovering the molecular machinery involved in creating the histone code, with diff fferent components serving as “writers,” “readers,” and “erasers” of chemi-
ra dcl iffe ma gazi ne Summer 2011
ONE of
Biology’s Youngest Fields
cal modifi fications. Recently, another layer of complexity has emerged: specific fi histone variants that also seem to help fine-tune the expression of genes. Collectively, this research reveals a stunning amount of complexity in how cells use their DNA. “This is probably how we had to evolve flexibility into the static DNA template,” Allis said. He pointed out that the field has come a long way since the first discoveries, in the mid-1990s. Since then, scientists have shown that epigenetic modifications fi are
important in many inherited diseases and in cancer. The first epigenetics-based drug was approved by the FDA in 2006, and the pharmaceutical industry is actively pursuing drugs that can alter histone modifi fications. All this suggests that understanding epigenetics may have practical benefits fi beyond the answers it provides to fundamental questions. ƒ Courtney Humphries is a freelance writer whose articles have appeared in the Boston Globe, Harvard Magazine, and other publications.
HOW DNA PACKAGING LEADS TO GENE EXPRESSION DNA is wound up with proteins called histones, creating chromatin. The structure of chromatin determines which genes are transformed into proteins and which lie dormant. Chromosome
Chromatin
Histones
DNA
Histone tails
Diagram g byy ed wiederer