Molecular Biology of the Cell track citations

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print November 28, 2007
Mol. Biol. Cell 10.1091/mbc.E07-04-0323

A more recent version of this article appeared on February 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E07-04-0323v1
19/2/608    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Casey, L.
Right arrow Articles by Fox, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Casey, L.
Right arrow Articles by Fox, C. A.

Submitted on April 10, 2007
Revised on September 19, 2007
Accepted on November 20, 2007

Conversion of a Replication Origin to a Silencer through a Pathway Shared by a Forkhead Transcription Factor and an S-Phase Cyclin

Laurieann Casey,* Erin E. Patterson,{dagger} Ulrika Müller,* and Catherine A. Fox*{dagger}

Department of *Biomolecular Chemistry and {dagger}Laboratory of Genetics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706

Monitoring Editor: Orna Cohen-Fix

Silencing of the mating-type locus HMR in S. cerevisiae requires DNA elements called silencers. To establish HMR silencing the Origin Recognition Complex binds the HMR-E silencer and recruits the Sir1 protein. Sir1 in turn helps establish silencing by stabilizing binding of the other Sir proteins, Sir2–4. However, silencing is semistable even in sir1{Delta} cells, indicating that SIR1-independent establishment mechanisms exist. Furthermore, the requirement for SIR1 in silencing a sensitized version of HMR can be bypassed by high-copy expression of FKH1 (FKH1hc), a conserved forkhead transcription factor, or by deletion of the S-phase cyclin CLB5 (clb5{Delta}). FKH1hc caused only a modest increase in Fkh1 levels but effectively reestablished Sir2–4 chromatin at HMR as determined by Sir3-directed chromatin immunoprecipitation. In addition, FKH1hc prolonged the cell cycle in a manner distinct from deletion of its close paralog FKH2, and created a cell cycle phenotype more reminiscent to that caused by a clb5{Delta}. Unexpectedly, and in contrast to SIR1, both FKH1hc and clb5{Delta} established silencing at HMR using the replication origins, ARS1 or ARSH4, as complete substitutes for HMR-E (HMR{Delta}E::ARS). HMR{Delta}E::ARS1 was a robust origin in CLB5 cells. However, initiation by HMR{Delta}E::ARS1 was reduced by clb5{Delta} or FKH1hc, while ARS1 at its native locus was unaffected. The CLB5-sensitivity of HMR{Delta}E::ARS1 did not result from formation of Sir2–4 chromatin since sir2{Delta} did not rescue origin firing in clb5{Delta} cells. These and other data supported a model in which FKH1 and CLB5 modulated Sir2–4 chromatin and late-origin firing through opposing regulation of a common pathway.

Address correspondence to: Catherine A. Fox (cfox{at}wisc.edu)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.