Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae

Knott, S. R. V., Peace, J. M., Ostrow, A. Z., Gan, Y., Rex, A. E., Viggiani, C. J., Tavaré, S., Aparicio, O. M. (January 2012) Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Cell, 148 (1-2). pp. 99-111. ISSN 00928674 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22265405
DOI: 10.1016/j.cell.2011.12.012

Abstract

The replication of eukaryotic chromosomes is organized temporally and spatially within the nucleus through epigenetic regulation of replication origin function. The characteristic initiation timing of specific origins is thought to reflect their chromatin environment or sub-nuclear positioning, however the mechanism remains obscure. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead regulation of origin timing is independent of local levels or changes of transcription. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. These findings add a new dimension to our understanding of the epigenetic basis for differential origin regulation and its connection to chromosomal domain organization. © 2012 Elsevier Inc.

Item Type: Paper
Uncontrolled Keywords: cell cycle protein forkhead transcription factor protein cdc45 transcription factor Fkh1 transcription factor Fkh2 unclassified drug article cell cycle G1 phase cell nucleus chromosome structure epigenetics eukaryote nonhuman nucleotide sequence priority journal protein domain protein protein interaction Saccharomyces cerevisiae transcription regulation
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Hannon lab
Depositing User: Matt Covey
Date: 20 January 2012
Date Deposited: 30 Jan 2013 19:47
Last Modified: 18 Mar 2015 13:37
PMCID: PMC3266545
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26978

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