Targeting Sir Proteins to Sites of Action: A General Mechanism for Regulated Repression (original) (raw)

1. M. COCKELL,
2. M. GOTTA,
3. F. PALLADINO,
4. S.G. MARTIN, and
5. S.M. GASSER
6. Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges/Lausanne, Switzerland

Excerpt

In yeast, a position-dependent chromatin-mediated silencing affects several regions of the genome, includingthe silent mating-type loci, telomeric regions, and rDNA.At HM and telomeric loci, repression requires a complexof the silent information regulator proteins (Sir2-Sir4p)that binds nucleosomes via the amino-terminal tails of histones H3 and H4. Nucleation of this complex requiresinteraction with sequence-specific DNA-binding proteins, among which figure Rap1, Abf1, and ORC. Weshow here that both the dosage and balance of Sir proteinsare critical for silencing. Different domains of thesehighly modular proteins are involved in regulating Sirprotein distribution among potential sites of repression.In particular, two factors that bind the amino-terminal271 amino acids of Sir4p (i.e., Sir1p, Sif2p) compete forlimiting pools of Sir factors, antagonizing the formationof repressed chromatin at telomeres. In contrast, the interaction of Ku70/80 with the carboxyl terminus of Sir4pappears to help recruit Sir proteins to telomeres and perhaps under specific conditions to internal sites...