Not simply passive barriers, insulators help organize and regulate gene activity by marking boundaries on chromatin, the condensed genetic material that forms chromosomes. By establishing chromatin boundaries, insulators can limit the range of action of other DNA elements that work to activate, or "turn on," the genes.
Recent studies on the LAT region of the HSV-1 genome have shown that nearby regions of the genome contain modifications indicative of silenced chromatin. The patterns found resemble well-studied regions where insulators are found in both yeast and chicken, namely the yeast mating loci and chicken globin locus.
To see if insulators play a role in silencing viral genes during the latent phase, Zhou and his group studied cells infected with HSV-1. The studies showed that during a latent period, the virus binds to a host protein called CTCF, a protein known to act as an insulator in mammals and in fruit flies. What's more, the findings revealed that the viral DNA binds to CTCF in the same manner as the host DNA binds to the protein.
"By binding in this manner, we believed the CTCF protein was interacting with other viral proteins to form a type of insulator in the virus structure," Zhou says.
To verify that it was an insulator at work, the researchers then inserted copies of the structure into fruit fly embryos to see if they could block the activity driven by gene-activating elements called "enhancers" during development.
"If the element we were testing was an insulator, then only one enhancer would be affected, and that's exactly what we found," Zhou says. Further studies showed that the insulator element blocked enhancer activities in the eye tissue of fruit flies and in human cells in culture.
"Based on these findings, we were able to identify this element as a kind of chromatin insulator that helps HSV-1 maintain a balance in its life cycle."
The study also s
'"/>
Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
2-May-2007