More about Epigenetics

Our bodies contain a multitude of cell types, such as brain, liver, and blood cells. All these cells share the exact same DNA; what makes every cell type unique is the way it uses the thousands of genes within its DNA. Epigenetic processes allow the body to turn on different subsets of genes in different cells at different times, allowing the various cell types to develop and function. A broad spectrum of diseases and behavioral patterns have been linked to the malfunctioning of epigenetic mechanisms — including almost all types of cancer; diseases of the respiratory, cardiovascular, reproductive, autoimmune, and nervous systems; and cognitive dysfunction.

At the molecular level, the processes by which genes are turned on or off are influenced by how DNA is spatially organized. The nucleus of a human cell contains around six feet of DNA that is packaged into an extraordinarily dense structure called chromatin. In this elaborate packaging process, DNA strands are wrapped around spool-shaped aggregates of proteins called histones. (When bundled up as chromatin, the six feet of DNA becomes a speck so small that it is invisible to the naked eye.)

To activate the expression of a particular gene, the cell “unwraps” DNA and histones to relax the chromatin surrounding the gene. This allows the machinery that transcribes or decodes DNA to gain access to the gene and turn it on.

Epigenetics and Cancer

We have recently learned that of the myriad biochemical processes that take place within cells, the unwrapping of chromatin is one of the most frequently mutated in tumor cells. When changes take place in the proteins that control chromatin structure — which may occur by two separate processes called DNA methylation and histone modification — numerous genes may be inappropriately activated or repressed and promote cancer.

Because some of these proteins can be inhibited with drugs, there is tremendous excitement about the possibility of developing a new class of cancer therapeutics that act by tweaking a cell’s chromatin structure to restore normal gene expression. In fact, a number of epigenetics-based drug molecules have already been developed and are currently being investigated in early-stage clinical trials at MSK.