Understanding the role of CpG islands in gene regulatory element function and transcription.

Every cell in the human body carries the same DNA, yet a skin cell and a liver cell behave completely differently—because different genes are switched on or off. This project investigates the tiny stretches of DNA called CpG islands that sit near the start of most genes and help control whether those genes are active. The problem is that scientists do not understand how CpG islands stay free of a chemical mark called DNA methylation, which would otherwise silence them. The researchers recently discovered that a family of proteins binds to unmethylated CpG islands and builds a special type of chromatin around them. This project will systematically map how CpG islands first establish and then maintain their unmethylated state, and how that state influences gene activity. This is fundamental science. It will not produce a drug or a diagnostic test next year. But gene regulation gone wrong lies at the heart of many diseases, including cancer, where CpG islands often become abnormally methylated. Understanding the basic mechanism could eventually point to new ways to detect or reverse those errors. Past discoveries in gene regulation—such as how DNA is packaged into chromatin—have already led to cancer therapies that target those same processes.