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Researchers Cracking the Human Genome Function

cts of genome function relate to one another.

The ENCODE project has given us unprecedented insight into how functional information is organized in the human genome, said Dr. John Stamatoyannopoulos, UW professor of genome sciences, one of the leaders of the ENCODE project, and a senior author on the Nature article. The diverse nature and sheer volume of the ENCODE data enabled us for the first time to visualize how the packaging of DNA, the replication of DNA, the production of RNA, and the evolution of DNA sequences all fit together.

Each ENCODE center used a different experimental approach for mapping functional sequences within the genome. The UW ENCODE team of molecular and computational biologists focused on identifying functional elements hidden in non-gene DNA by carefully mapping how DNA is packaged in the cell nucleus.

In order to fit within the nucleus, DNA is tightly wound around proteins to create a substance called chromatin. Many years ago, researchers found differences between the chromatin at gene-controlling DNA sequences and the chromatin in other areas of the genome. In these gene-controlling regions, specialized proteins latch onto DNA and unfold the chromatin, activating nearby genes.

The UW team created new methods for finding these unfolded regions within the billions of DNA bases on the genome. First, they used an inexpensive enzyme, called DNaseI, as a molecular bloodhound. When it is injected into a living cell, the enzyme seeks out regions of unfolded chromatin that correspond to functional elements. By mapping where the DNaseI traveled, the researchers created a high-resolution map of chromatin structure that pinpointed the locations of thousands of gene-controlling sequences.

To handle the massive amounts of data produced by the many ENCODE teams, Stamatoyannopoulos teamed up with Dr. William Noble, UW associate professor of genome sciences and computer science. Together
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