Scientists Find Genome Structure Responsible for Gene Activation

The first high-resolution analysis of the key feature that controls the activation of genes on human chromosomes was reported today in the journal Cell, by researchers from the Broad Institute of MIT and Harvard and Affymetrix.

The study is pioneering in its large scale and surprising in its results. It reveals previously unknown domains of gene regulation in human chromosomes and also suggests the existence of many novel functional elements in the human genome.

The research team used Affymetrix GeneChip microarrays, each containing millions of distinct DNA fragments to examine "chromatin," the intricate structure that packages the genome and makes certain genes accessible and others inaccessible to the cell. Using these microarrays, the researchers surveyed two entire human chromosomes (chromosomes 21 and 22) as well as additional regions in both the human and mouse genomes.

Despite rapid progress in identifying human genes based on the completed sequence of the human genome, the genome's complex regulatory network — the mechanisms that turn genes on and off — still remains poorly understood. "Chromatin is a key part of the regulatory network that controls how genetic information is translated into a cell or an organism. Understanding chromatin is important because many of its components are implicated in cancer and other diseases," said Brad Bernstein, a research associate at the Broad Institute and instructor of pathology at Harvard Medical School, who co-led the study.

With the ability to perform genome-wide analysis, it should now become possible to gain very general insight into the structure and function of chromatin, said the researchers. In particular, such studies may be useful for understanding how gene regulation becomes defective in certain diseased tissues and cells, they said.