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)
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: |
https://repository.cshl.edu/id/eprint/26978 |
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