The new study, which looks at these areas at high resolution in cells of the different blood cell lineages and in blood stem cells, finds that in many cases, a core portion of the unmethylated region is shared in common, but that adjacent areas, sometimes called "CpG shores" the outlying areas around CpG islands differ markedly in breadth. The CSHL-USC team refines the notion of islands and shores, preferring to describe the narrowing and widening of the "shoreline" as a tidal phenomenon.
"We observed that the boundaries of these unmethylated regions goes in and out, like the tides," says Hodges. "The key question is what drives these changes. We found that the width of these regions depends on the gene that is associated with the region. We showed in blood cells that the variation is lineage-specific."
The team deduced this after making close study of the methylation patterns in genomic regions containing genes known from other research to be expressed specifically in lymphoid cells, but not in myeloid cells, or vice versa. In these cases, all blood cells share a narrow "core" region of hypomethylation; but only in one lineage did the unmethylated region widen a widening that opens the promoter of the "underlying" gene to the cellular machinery initiating gene expression. In other words, the lack of methylation over a wider area enables the underlying gene to be activated only in the specified cell-type, but not in any of the others.
Another striking observation made from this data is the directional preference of this expansion. For example, in the widening of the unmethylated region seen in the case of the lymphoid cell, the direction of the widening was toward the area occupied by the underlying gen
|Contact: Peter Tarr|
Cold Spring Harbor Laboratory