Both groups used fluorescence recovery after photobleaching (FRAP) to track the behavior of heterochromatin protein 1 (HP1). HP1 was not static but moving around, as Misteli puts it, in the “same sort of range” as transcription factors.
Although both groups found that HP1 was dynamic, Festenstein's mobility values were lower than those found by Misteli. Part of the difference may lie in varying bleaching and microscopy methods, but both researchers suggest the importance of the different cell types used. Festenstein looked in primary T cells—a resting cell type—and when he stimulated the T cell receptor to activate these cells, his new values for HP1 mobility increased almost to the level seen by Misteli in his transformed cells. Thus, an increase in heterochromatin protein dynamics may help kick-start a T cell as it takes on invading microbes.
The details of how cell activation increases mobility remain to be determined, but the overall high level of mobility is already causing a rethinking of standard models of heterochromatin. The important point, says Misteli, is not to confuse stable with static. “We think most stable structures are dynamic,” he says. “You can generate stable structures from dynamic components.” The dynamic behavior may, however, indicate that dimers or small oligomers of HP1 may be the building blocks of heterochromatin, rather than the large oligomeric networks portrayed in many textbooks.
Also up for grabs is the accessibility of both heterochromatic DNA and the ever-important histone tails (the target of HP1 binding). With the dynamic behavior of HP1, says Festenstein, “now you get an opportunity for access.” Thus, heterochromatin is not dormant but subject to constant competition for binding between HP1 and the activators and remodeling factors that seek to bring DNA into the open. ▪