Fkh1 and Fkh2 bind multiple chromosomal elements in the S. cerevisiae genome with distinct specificities and cell cycle dynamics

Ostrow, A. Z., Nellimoottil, T., Knott, S. R., Fox, C. A., Tavare, S., Aparicio, O. M. (2014) Fkh1 and Fkh2 bind multiple chromosomal elements in the S. cerevisiae genome with distinct specificities and cell cycle dynamics. PLoS One, 9 (2). e87647. ISSN 1932-6203

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URL: http://www.ncbi.nlm.nih.gov/pubmed/24504085
DOI: 10.1371/journal.pone.0087647

Abstract

Forkhead box (FOX) transcription factors regulate a wide variety of cellular functions in higher eukaryotes, including cell cycle control and developmental regulation. In Saccharomyces cerevisiae, Forkhead proteins Fkh1 and Fkh2 perform analogous functions, regulating genes involved in cell cycle control, while also regulating mating-type silencing and switching involved in gamete development. Recently, we revealed a novel role for Fkh1 and Fkh2 in the regulation of replication origin initiation timing, which, like donor preference in mating-type switching, appears to involve long-range chromosomal interactions, suggesting roles for Fkh1 and Fkh2 in chromatin architecture and organization. To elucidate how Fkh1 and Fkh2 regulate their target DNA elements and potentially regulate the spatial organization of the genome, we undertook a genome-wide analysis of Fkh1 and Fkh2 chromatin binding by ChIP-chip using tiling DNA microarrays. Our results confirm and extend previous findings showing that Fkh1 and Fkh2 control the expression of cell cycle-regulated genes. In addition, the data reveal hundreds of novel loci that bind Fkh1 only and exhibit a distinct chromatin structure from loci that bind both Fkh1 and Fkh2. The findings also show that Fkh1 plays the predominant role in the regulation of a subset of replication origins that initiate replication early, and that Fkh1/2 binding to these loci is cell cycle-regulated. Finally, we demonstrate that Fkh1 and Fkh2 bind proximally to a variety of genetic elements, including centromeres and Pol III-transcribed snoRNAs and tRNAs, greatly expanding their potential repertoire of functional targets, consistent with their recently suggested role in mediating the spatial organization of the genome.

Item Type: Paper
Uncontrolled Keywords: Binding Sites Cell Cycle/*physiology Cell Cycle Proteins/*metabolism Chromatin Immunoprecipitation *Chromosomes, Fungal Forkhead Transcription Factors/*metabolism Gene Expression Regulation, Fungal *Genome, Fungal Nucleosomes/metabolism Protein Binding *Regulatory Sequences, Nucleic Acid Replication Origin Saccharomyces cerevisiae/*genetics/*metabolism Saccharomyces cerevisiae Proteins/*metabolism
Subjects: bioinformatics
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
organism description > yeast
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Hannon lab
Depositing User: Matt Covey
Date: 2014
Date Deposited: 18 Mar 2015 14:52
Last Modified: 18 Mar 2015 14:52
PMCID: PMC3913637
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31275

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