Figure 1

Model for de novo heterochromatin formation of RIP’d sequences. Mutations by RIP typically create an AT-rich cis-acting signal for de novo heterochromatin formation. In the upper section, DNA is shown wrapped around green nucleosomes with a region of RIP’d DNA represented in red and flanking unRIP’d DNA in black. The double arrow and associated question mark (?) represent the recognition of the RIP’d DNA by one or more unknown factors important for the initial step(s) in the establishment of heterochromatin. In the middle section, a sequence of events is depicted on a representative nucleosome from the RIP’d region. The cell cycle regulated H3S10p (yellow lollipops) is a posttranslational modification that is inhibitory to both the action of the DIM-5 complex (red oval with unidentified members of the complex represented by the ‘?’) and to the binding of the chromo-domain protein HP1 (green oval). Removal of H3S10p by the phosphatase, PP1 (orange oval), allows the DIM-5 complex to trimethylate H3K9 (red triple-headed lollipops) and initiate heterochromatin formation. HP1 binds to the H3K9me3 through its chromo-domain and recruits the DNA methyltransferase DIM-2 (blue oval) through a direct interaction of its chromo-shadow domain with two PXVXL-related motifs in DIM-2. DIM-2 methylates any cytosine residue (white circles) within the associated RIP’d DNA. In the bottom section, the fully modified RIP’d region is depicted in a more condensed state with bound HP1 concentrated at the flanks of the region where it recruits the DMM complex (light blue oval). The DMM complex prevents the heterochromatin from spreading into neighboring unRIP’d DNA by inhibiting H3K9me3.