We show that the budding yeast protein Chl1p, required for sister-chromatid cohesion, also modulates transcriptional silencing at HMR and telomeres. The absence of this protein results in increased silencing at HMR and, conversely, in decreased silencing at the telomere. The regulation of silencing by Chl1p at these two loci is dependent on the presence of Sir proteins. Chl1p also acts synergistically with Sir2p to suppress rDNA recombination. In the absence of this protein, yeast cells exhibit reduced life span and hypersensitivity to heat stress. These observations suggest a role of Chl1p in regulating chromatin structure. (c) 2005 Elsevier Inc. All rights reserved.