Mechanisms of heterochromatin subnuclear localization

• A new role for histone modifications in determining the nuclear organization of heterochromatin.
• Many aspects are conserved from worms to man.
• A model for self-propagating perinuclear foci of repressed chromatin is proposed.

Transcriptionally repressed heterochromatin becomes the dominant form of chromatin in most terminally differentiated cells. Moreover, in most cells, at least one class of heterochromatin is positioned adjacent to the nuclear lamina. Recent approaches have addressed the mechanism of heterochromatin localization, in order to determine whether spatial segregation contributes to gene repression. Findings in worms and human cells confirm a role for histone H3K9 methylation in heterochromatin positioning, identifying a modification that is also necessary for gene repression of worm transgenic arrays. These pathways appear to be conserved, although mutations in mammalian cells have weaker effects, possibly due to redundancy in positioning mechanisms. We propose a general model in which perinuclear anchoring is linked to an epigenetic propagation of the heterochromatic state, through histone modification.