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| Status |
Public on Mar 09, 2017 |
| Title |
Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae (HTS) |
| Organism |
Saccharomyces cerevisiae |
| Experiment type |
Other
|
| Summary |
Forkhead Box (Fox) proteins share the Forkhead domain, a winged-helix DNA binding module, which is conserved among eukaryotes from yeast to humans. These sequence-specific DNA binding proteins have been primarily characterized as transcription factors regulating diverse cellular processes from cell cycle control to developmental fate, deregulation of which contributes to developmental defects, cancer, and aging. We recently identified S. cerevisiae Fkh1 and Fkh2 as required for the clustering of a subset of replication origins in G1 phase and for the early initiation of these origins in the ensuing S phase, suggesting a mechanistic role linking the spatial organization of the origins and their activity. Here we show that Fkh1 and Fkh2 share a unique structural feature of human FoxP proteins that enables FoxP2 and FoxP3 to form domain-swapped dimers capable of bridging two DNA molecules in vitro. Accordingly, Fkh1 self-associates in vitro and in vivo in a manner dependent on the conserved domain-swapping region, strongly suggestive of homo-dimer formation. Fkh1- and Fkh2-domain-swap-minus (dsm) mutations are functional as transcription factors yet are defective in replication origin timing control. Fkh1-dsm binds replication origins in vivo but fails to cluster them, supporting the conclusion that Fkh1 and Fkh2 dimers perform a structural role in the spatial organization of chromosomal elements with functional importance.
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| Overall design |
S. cerevisiae strains with various Forkhead protein mutations and deletions were examined by BrdU-IP-Seq, RNA-Seq, and 4C-Seq.
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| Contributor(s) |
Ostrow AZ, Kalhor R, Gan Y, Villwock SK, Christian L, Matteo B, Chen L, Aparicio OM |
| Citation(s) |
28265091 |
| |
| Submission date |
Feb 10, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Andrew Zachary Ostrow |
| E-mail(s) |
aostrow@usc.edu
|
| Organization name |
University of Southern California
|
| Department |
Biological Sciences
|
| Lab |
Oscar Aparicio
|
| Street address |
1050 Childs Way
|
| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90089 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13821 |
Illumina HiSeq 2000 (Saccharomyces cerevisiae) |
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| Samples (22)
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| This SubSeries is part of SuperSeries: |
| GSE94796 |
Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae |
|
| Relations |
| BioProject |
PRJNA374346 |
| SRA |
SRP099233 |
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