Heterochromatin protein 1 (HP1) is generally considered as the 'keeper' of heterochromatin — transcriptionally silenced, condensed DNA that is also typically associated with the centromeric regions. It is thought to do this by crosslinking chromatin, thereby creating a dense chromatin environment that is impermeable to transcriptional activators. Two papers, published in Science, from teams led by Richard Festenstein and Tom Misteli, now challenge this view.

Both groups studied the dynamics of HP1 — a major component of heterochromatin — using fluorescence recovery after bleaching (FRAP) on cells that express green fluorescent protein (GFP)–HP1 isoform α, β or γ fusion proteins. Misteli and colleagues stably transfected immortalized Chinese hamster ovary (CHO) cells, whereas the Festenstein group generated transgenic mice that expressed GFP–HP1β isoform protein specifically in T cells.

In CHO cells, fluorescence recovery was rapid for all HP1 isoforms; complete recovery was reached within 5 s in less dense euchromatin and within ∼60 s in heterochromatin. In resting T cells taken from the transgenic mice, recovery was much slower and incomplete; ∼70% was recovered in 150–200 s in heterochromatin, and ∼90% in 90–100 s in euchromatin. HP1 mobility in heterochromatin was reduced compared with euchromatin, which possibly reflects the higher density of HP1-binding sites in heterochromatin. Incomplete recovery in resting T cells indicates the presence of an immobile fraction of HP1β molecules, which is larger in heterochromatin than in euchromatin.

To examine the effects of T-cell activation — which triggers gene activation and cell-cycle induction — on HP1 mobility, Festenstein and colleagues measured FRAP in T cells that were taken from mice and activated ex vivo. GFP–HP1β mobility was significantly increased, both in heterochromatin and euchromatin, compared with unstimulated cells. Moreover, the immobile HP1β fraction in heterochromatin was reduced to ∼10%. The recovery time in heterochromatin in activated T cells (50–80 s) was similar to that in CHO cells (∼60 s), and the fluorescence recovery was indeed almost complete — as in CHO cells.

So, it seems that HP1 binds transiently to heterochromatin and euchromatin, which leads the authors to conclude that heterochromatin is not inaccessible to other factors, and that the continuous exchange of HP1 allows transcriptional regulators to compete for binding, thereby determining the fate of the heterochromatin region. In addition, the increased mobility of HP1 in immortalized cells and activated T cells allows the heterochromatin to be restructured, which might facilitate cell-cycle entry and transcriptional activation.