The big switch
Epigenetics gains ground at Dana-Farber
By Robert Levy
Some gene activity is controlled by a process called DNA methylation, in which chemical compounds called methyl groups (shown in red and yellow) attach and detach from key portions of genes. Another control mechanism is known as chromatin remodeling, in which proteins called histones (in blue) cause changes in the way DNA is packaged in the cell nucleus.
Illustration by John DiGianni and Amelia Lepak
The script of a cancer cell's life seems to have been written by a scatterbrain. Genes that normally issue precise commands for cell division begin flubbing their lines. Other genes – the molecular equivalent of nervous nellies – speak in letter-perfect sentences but at inappropriate times, or with too much or too little emphasis. Imagine an actor barking military orders during a tender love scene, and it's clear how jarring such mistakes can be.
Cancer is generally thought of as a disease of broken genes – misspellings in DNA that cause defective proteins to be produced and cell growth to go haywire. However, the actual mechanics of the disease are more subtle and complicated.
It turns out that even normal genes, which harbor no abnormalities, or mutations, in their DNA, can cause problems if they are active when they should be idle, or if they're working too little or too much. The system for switching genes on and off without changing their basic sequence is known as "epigenetics."
Thanks to new technology for surveying these switches across the genome, epigenetics is earning increased attention among researchers in cancer and other fields. At Dana-Farber, it is the subject of renewed focus as well.
Epigenetics helps explain why we are complex assemblages of different tissues and organs, rather than anonymous blobs of identical cells.
Though rarely taught in undergraduate biology courses, epigenetics is essential for understanding why we are complex assemblages of different tissues and organs, rather than anonymous blobs of identical cells. Every cell in the body carries the exact same genetic programming, yet a brain cell is clearly different from a liver, bone, or blood cell, or any of the other 200-odd cell types in human beings. During embryonic and fetal development, certain sets of genes are turned on and off in a complex process that molds the cell's identity and determines its function. It's as though an automaker dipped into the same parts catalogue to produce a sports car, a minivan, and a pickup truck. Epigenetics ensures that cells "remember" who they are, and pass that identity on when they divide.
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