Topic: Epigenetics

Yellow bands indicate where a gene-silencing protein docks to a target on chromatin, the tightly compacted complex of DNA and histone proteins in the cell's nucleus.

Epigenetics is a field of research that explores the inheritance of physical changes that cannot be traced back to mutations in the DNA sequence. It is now widely accepted that such non-DNA encoded heritable information has important implications for human biology and human disease, especially cancer.

The double helix structure of DNA actually is tightly coiled in a Slinky-like manner around protein "spools" called histones. The coiled DNA and histones together form a largely protective and highly constrained structure called chromatin. Poking through this tightly folded complex are long flexible proteins — the histone tails.

Rockefeller’s C. David Allis has been a leader in the field of epigenetics. In 2000, Allis and Brian Strahl first proposed what has now been referred to as the "histone code." According to their hypothesis, chemical modifications of the histone tails play a vital role in determining which genes are turned on or off. These modifications, which attach certain chemical groups to specific amino acids (the building blocks of proteins) on the histone tails, act like flags to direct the docking of other important proteins, some of which open up the tightly wrapped DNA, providing access to genes. Research by Allis and his colleagues at Rockefeller has identified a number of enzymes that “read,” “write” and “erase” the histone code. The findings have broadened our understanding of how embryos develop and how diseases, such as cancer, arise.

Scientists at Rockefeller have shown that histone modifications play crucial roles in mental retardation and drug addiction and they guide the development and differentiation of epidermal skin stem cells in mouse embryos, which temper the development of the skin barrier. Rockefeller researchers have mapped epigenetic changes that are likely to play a role in initiating the transcription of genes in Trypanosoma brucei, the deadly single-celled parasite responsible for African sleeping sickness. Other scientists studying epigenetics have shown that the core tenets of the histone code are universal, and they have identified a synthetic histone mimics that block inflammation and viral infections.