Sir4

Sir4, short for Silent Information Regulator 4, is a chromatin-associated protein in the budding yeast Saccharomyces cerevisiae. It is a central component of the SIR (Sir2/3/4) complex, which also includes Sir2 and Sir3. This complex mediates transcriptional silencing at telomeres and at the silent mating-type loci HML and HMR by establishing a condensed, heterochromatin-like chromatin state that is less accessible to transcription factors.

Sir4 acts as a scaffold for the complex, mediating interactions between Sir2, Sir3, and chromatin. It helps recruit the SIR complex to silencers and to telomeres and participates in spreading silencing along subtelomeric regions. At telomeres, interactions with Rap1 help anchor the complex, stabilizing silent chromatin. Sir2 deacetylates histone tails, and the deacetylated nucleosomes promote Sir3 and Sir4 binding, reinforcing the silent state.

Genetic analyses show that loss of Sir4 compromises silencing at telomeres and HM loci and reduces the heritability of the silent chromatin state across cell divisions. Sir4 mutants often display derepression of subtelomeric genes and loss of mating-type silencing, highlighting its role in maintaining epigenetic memory.

Discovery and naming: The Silent Information Regulator genes were identified in the late 1980s as regulators of transcriptional silencing in yeast. Sir4 is one of the core components of the SIR silencing system and is essential for establishing and maintaining heritable silent chromatin at specific chromosomal regions.