Although every cell of our bodies contains the same genetic instructions, specific genes typically act only in specific cells at particular times. Other genes are "silenced" in a variety of ways. One mode of gene silencing depends upon the way DNA, the genetic material, is packed in the nucleus of cells.
When packed very tightly around complexes of proteins called histones, the DNA double helix is rendered physically inaccessible to molecules that mediate gene expression. Now, a research team that includes Michael Q. Zhang, Ph.D., a professor at Cold Spring Harbor Laboratory (CSHL), has published a comprehensive analysis of modification patterns in histones.
Using a new technology called ChIP-Seq, the team identified 39 histone modifications, including a "core set" of 17 modifications that tended to occur together and were associated with genes observed to be active.
Modification Patterns With Different "Personalities"
Scientists have long known that chemical changes at particular locations in histone complexes influence how tightly the DNA is wrapped around the histones. "But it is important to know whether particular modifications occur together in characteristic patterns, or if these patterns can predict gene activities," Dr. Zhang explained.
At the heart of the team's efforts to determine this, Keji Zhao, Ph.D., of the National Heart, Blood, and Lung Institute of the National Institutes of Health, and his colleagues developed a method to map modifications in human white blood cells known as CD4+ T cells. First they used an enzyme to cut the DNA into short segments, which remained attached to histone "spools." For each of 39 distinct histone modifications, the scientists used an antibody to extract matching histone-DNA combinations. Finally, they used the ChIP-Seq DNA-sequencing technology to determine which parts of the genome were bound to each type of modified histone.
The team's most recent
|Contact: Jim Bono|
Cold Spring Harbor Laboratory