Figure 7.

A competition model for positive and negative roles of euchromatic histone modifications in heterochromatin formation. Euchromatic histone modifications can have positive roles (arrows) and negative roles (blunt arrows) in heterochromatin formation. Competition between euchromatic histone modifiers and heterochromatin proteins for interactions with nucleosomes can occur at three locations and can have different outcomes (see text). 1) Competition within heterochromatin regions creates a semi-stable epigenetic state. 2) Competition at the interface between euchromatin and heterochromatin prevents local spreading of the Sir complex, thereby on the one hand avoiding ectopic silencing of regions adjacent to heterochromatin and on the other hand ensuring availability of limiting silencing proteins for the endogenous heterochromatic regions. 3) Competition throughout euchromatin prevents non-specific binding of the Sir2/3/4 complex to bulk chromatin, thereby enhancing targeting of Sir proteins to endogenous heterochromatic regions to ensure sufficient spreading of the Sir complex. By these mechanisms, the function of a euchromatic histone modification in gene silencing depends on the relative contribution that it makes to each of these mechanisms and to what extend the negative and positive functions counteract each other.