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Originally published as MBoC in Press, 10.1091/mbc.E08-01-0099 on November 12, 2008

Vol. 20, Issue 2, 631-641, January 15, 2009

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Subtelomeric ACS-containing Proto-silencers Act as Antisilencers in Replication Factors Mutants in Saccharomyces cerevisiae

Muhammad Attiq Rehman*, Dongliang Wang*, Genevieve Fourel{dagger}, Eric Gilson{dagger}, and Krassimir Yankulov*

*Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada; and {dagger}Laboratoire de Biologie Moléculaire de la Cellule de l'Ecole Normale Supérieure de Lyon, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5161, F-69364, Lyon, France

Submitted February 8, 2008; Revised October 1, 2008; Accepted November 4, 2008
Monitoring Editor: Yixian Zheng

Subtelomeric genes are either fully active or completely repressed and can switch their state about once per 20 generations. This meta-stable telomeric position effect is mediated by strong repression signals emitted by the telomere and relayed/enhanced by weaker repressor elements called proto-silencers. In addition, subtelomeric regions contain sequences with chromatin partitioning and antisilencing activities referred to as subtelomeric antisilencing regions. Using extensive mutational analysis of subtelomeric elements, we show that ARS consensus sequence (ACS)-containing proto-silencers convert to antisilencers in several replication factor mutants. We point out the significance of the B1 auxiliary sequence next to ACS in mediating these effects. In contrast, an origin-derived ACS does not convert to antisilencer in mutants and its B1 element has little bearing on silencing. These results are specific for the analyzed ACS and in addition to the effects of each mutation (relative to wild type) on global silencing. Another line of experiments shows that Mcm5p possesses antisilencing activity and is recruited to telomeres in an ACS-dependent manner. Mcm5p persists at this location at the late stages of S phase. We propose that telomeric ACS are not static proto-silencers but conduct finely tuned silencing and antisilencing activities mediated by ACS-bound factors.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-01-0099) on November 12, 2008.

Address correspondence to: Krassimir Yankulov (yankulov{at}uoguelph.ca)

Abbreviations used: ACS, ARS consensus sequence; FOA, fluoroorotic acid; MCM, minichromosome maintenance; ORC, origin recognition complex; STAR, subtelomeric antisilencing region; TPE, telomeric position effect.






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