Tuesday, August 4, 2015
Molecular biologist Iestyn Whitehouse studies how modification patterns in DNA and the proteins that make up chromosomes determine which genes are expressed — used to make proteins — and which ones are ignored.
- Histones are the proteins that help package DNA.
- DNA and histones together make up chromatin, the material of chromosomes.
- Changes in chromatin determine which genes are expressed in cells.
- C. elegans, a transparent nematode worm, is a useful model system.
The body contains roughly 200 different types of cells, which range in function from bone to liver to nerve to skin. But as different as they are, each of these cell types shares the same DNA.
The system that makes it possible for cells that have the same genome to be so different is the epigenome, which is made up of molecular markers that tell each cell which genes to translate into proteins and which ones to ignore. The two most well-studied methods for marking DNA are the attachment of small molecules — called methyl groups — to DNA and the modification of histones, proteins that form the structures around which DNA is wrapped.
Searching for Patterns
MSK molecular biologist Iestyn Whitehouse studies chromatin, the assemblage of DNA and histones that makes up chromosomes. In particular, his lab is looking at how specific patterns of DNA and histone modifications — which are known as chromatin states — determine whether a gene is expressed, or used to make a protein.
“There are specific modifications associated with particular genomic functions and different types of gene expression,” he explains. “For example, if a gene is actively expressed, it will have a certain modification pattern, or chromatin state. If a gene is repressed, it will have a different modification pattern.”
When cells divide, or replicate, their patterns of gene expression are usually passed on from the parent cell to the two daughter cells. “One of the things we’re looking at is how that global process of cell division relates to chromatin: How does the cell remember what it was before, and how are chromatin states passed down from one cell generation to the next?” Dr. Whitehouse says.
Exactly how this information is passed down is an important area of research, and one that isn’t yet fully understood. “We know about some of the enzymes that maintain these chromatin states,” he notes, “but there is still much to learn. We’re not sure about the mechanism by which chromatin remembers what it used to be before cell division and what the copying mechanism is for chromatin in the new daughter cells.”Back to top
A “Neat” Model System
From an evolutionary perspective, the structure of chromatin is well conserved, which means that it has changed little between simpler organisms — such as yeast and Caenorhabditis elegans, a transparent nematode worm — and more complex organisms, including humans.
“In our lab we use C. elegans, which is a very neat model system because you can follow it from an early embryo as it develops into an adult and see all the developmental pathways and cell specializations that occur,” Dr. Whitehouse says. “Many of the advances in our understanding of chromatin have been possible because of work in these simpler organisms, and the findings have now been translated to research in human cells.”
Although changes in the epigenome (known as epigenetic changes) are a normal part of many biological processes — for example, allowing stem cells to differentiate into more-specialized cell types — they also can lead to cancer and other diseases.
“One way to think of cancer is the cell’s developmental processes have gone haywire,” Dr. Whitehouse says. “In order to understand how these changes occur in cancer and how we might reverse them with drugs, we first need to get a better understanding of how chromatin states function and are maintained in normal cells.”Back to top