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GENES & DEVELOPMENT 19:1811-1822, 2005
©2005 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH PAPER

Control of replication initiation and heterochromatin formation in Saccharomyces cerevisiae by a regulator of meiotic gene expression

Horst Irlbacher1,3, Jacqueline Franke1,3, Thomas Manke2, Martin Vingron2 and Ann E. Ehrenhofer-Murray1,3,4

1 Otto-Warburg-Laboratorium and 2 Department for Computational Molecular Biology, Max-Planck-Institut für Molekulare Genetik, D-14195 Berlin, Germany; 3 Institut für Genetik, Justus-Liebig-Universität Giessen, D-35392 Giessen, Germany

Heterochromatinization at the silent mating-type loci HMR and HML in Saccharomyces cerevisiae is achieved by targeting the Sir complex to these regions via a set of anchor proteins that bind to the silencers. Here, we have identified a novel heterochromatin-targeting factor for HML, the protein Sum1, a repressor of meiotic genes during vegetative growth. Sum1 bound both in vitro and in vivo to HML via a functional element within the HML-E silencer, and sum1{Delta} caused HML derepression. Significantly, Sum1 was also required for origin activity of HML-E, demonstrating a role of Sum1 in replication initiation. In a genome-wide search for Sum1-regulated origins, we identified a set of autonomous replicative sequences (ARS elements) that bound both the origin recognition complex and Sum1. Full initiation activity of these origins required Sum1, and their origin activity was decreased upon removal of the Sum1-binding site. Thus, Sum1 constitutes a novel global regulator of replication initiation in yeast.

[Keywords: HML-D; Hst1; chromatin; replication; origin; ARS]

Received December 17, 2004; revised version accepted June 1, 2005.


Supplemental material is available at http://www.genesdev.org.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.334805.

4 Corresponding author.
E-MAIL ehrenhof{at}molgen.mpg.de; FAX 49-30-8413-1130.


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