Bernstein and Schreiber began to develop the analytical techniques several years earlier, working with the smaller yeast genome. To investigate the much larger human genome, they collaborated with Affymetrix. They isolated the DNA regions with certain major methyl and acetyl tags, and used new microarray technology to identify the underlying genetic sequences associated with the tagged chromatin. Next, they teamed up with Michael Kamal, the co-first author of the paper, Eric Lander, and their Broad Institute colleagues, for the daunting computational analysis required to interpret the resulting data.
In most cases, the mapped tags coincided with the transcription starting points of active genes, as they and others had seen earlier in the yeast. Unexpectedly, they also found tags idling over regions near genes. The researchers think these sites have important regulatory functions, because the methylation patterns are similar in comparable portions of the mouse genome. Until now, they'd been missed by more standard genome analysis tools.
Most exciting to Bernstein is the unusual density of histone tags spread over the regions of genome containing the HOX genes, which are key regulators of development.
"In most of the genome, we see short stretches associated with activated histones," Bernstein said. "However, in the HOX regions, we see huge stretches of genome, many thousands of base pairs in length, that are completely covered by tags." The researchers speculate that these unique chromatin structures could be activating sets of HOX genes for specific developmental programs.
This global activation may have implications for understanding mechanisms behind certain cancers, Bernstein believes. For example, proteins that place methyl groups on histones can, when mutated, cause leukemia. Bernstein hopes to apply
Source:Howard Hugues Medical Institute