text: SIR4 is involved in scaffolding the assembly of silenced chromatin. It binds to DNA with high affinity, but low specificity. It is most stable when co-expressed with SIR2, but neither SIR2 nor SIR3 are required for it to operate at the telomeres. Each half of the SIR4 protein has distinct responsibilities in heterochromatin spreading. SIR4s N-terminus is required for telomeric silencing, but not for homothallic mating-type (HM) silencing. Conversely, its C-terminus supports HM but not telomeric repression. The N-terminus is positively charged and can be recruited to the telomeric repression site by SIR1 and YKU80. The C-terminus contains the coiled-coil region, which interacts with SIR3 in the heterotrimeric SIR complex and can also interact with RAP1 and YKU70 for recruitment to the telomeric region of the chromosome. The C-terminus also contains the SIR2-interacting domain (SID), where SIR4 can bind to the extended N-terminus of SIR2. SIR2 can catalyze reactions without being bound to SIR4, but SIR2s catalytic activity is enhanced when interacting with SIR4.