FKH1/YIL131C Summary Help

Standard Name FKH1 1
Systematic Name YIL131C
Feature Type ORF, Verified
Description Forkhead family transcription factor; minor role in expression of G2/M phase genes; negatively regulates transcription elongation; positive role in chromatin silencing at HML, HMR; facilitates clustering and activation of early-firing replication origins; binds to recombination enhancer near HML, regulates donor preference during mating-type switching; relocalizes to cytosol in response to hypoxia; FKH1 has a paralog, FKH2, that arose from the whole genome duplication (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and see Summary Paragraph)
Name Description ForK head Homolog 1
Chromosomal Location
ChrIX:102235 to 100781 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All FKH1 GO evidence and references
  View Computational GO annotations for FKH1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 857 genes
Regulators 1 genes
Resources
Classical genetics
null
Large-scale survey
null
overexpression
Resources
118 total interaction(s) for 95 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 29
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 6
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Growth Defect: 4
  • Dosage Rescue: 4
  • Negative Genetic: 26
  • Phenotypic Enhancement: 16
  • Phenotypic Suppression: 9
  • Positive Genetic: 20
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 484
Molecular Weight (Da) 53,490
Isoelectric Point (pI) 8.49
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIX:102235 to 100781 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 1994-12-10 | Sequence: 1994-12-10
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1455 102235..100781 1994-12-10 1994-12-10
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001393
SUMMARY PARAGRAPH for FKH1

FKH1 is a member of the winged-helix/forkhead (FOX) transcription factor gene family that regulates the expression of the CLB2 cluster of genes during the G2/M phase of the mitotic cell cycle (reviewed in 12 and 13). The CLB2 cluster of genes includes mitotic regulators such as CLB1, CLB2, CDC5 and CDC20 as well as SWI5 and ACE2, transcription factors required for the subsequent temporal wave of cell cycle regulated gene expression in the M/G1 phase interval (14). FHK1 and FKH2 appear to have partially redundant roles in the activation and periodic regulation of genes in the CLB2 cluster based on phenotypes associated with the double deletion strain (2, 15, 3, 1). Strains deleted for both genes also display morphological alterations including defects in cell separation, budding, and the induction of a nutrient-independent pseudohyphal-like growth phenotype that can be suppressed by multicopy CLB2 (2, 15, 3, 1). However, Fkh1p and Fkh2p have distinct functions in the control of G2/M phase transcription and regulation of the cell cycle (2, 15, 3, 1). First, strains deleted for FKH1 alone display enhanced transcription of CLB2 throughout the cell cycle and a slightly elevated rate of progression through the S and G2/M phases of the cell cycle (1). In contrast, FKH2 deletion strains display reduced CLB2 transcription and a reduced rate of progression through the cell cycle (1). Second, Fkh2p (but not Fkh1p) has been identified as a component of Swi-five factor, a factor known to form constitutive ternary complexes with Mcm1p on relevant promoters, as a prerequisite step for the later recruitment of the rate-limiting transcriptional coactivator Ndd1p (15, 3, 16). Third, Fkh1p and Fkh2p display differential promoter occupancy in vivo, and in many cases compete for target promoter occupancy; purified Fkh2p, but not Fkh1p, binds to promoters in a cooperative manner with Mcm1p in vitro (4). Fourth, Fkh1p cooperates with Isw1p to remodel chromatin and repress transcription of CLB2 during G2/M, while Fkh2p cooperates with Isw2p to remodel chromatin and repress CLB2 transcription during G1 phase (17). Finally, Fkh1p and Fkh2p associate with the coding region of active genes where they regulate transcriptional elongation and termination in opposing ways by affecting the phosphorylation status of the C-terminal repeat domain (CTD) of RNA Polymerase II (6).

FKH1 has additional roles in the establishment of a silenced state at HMRa, one of two silent mating type loci, and in the regulation of donor preference during mating type switching. FKH1 was identified as a high-copy-number suppressor of a hypomorphic allele of SIR1, a gene required to establish silencing at the silent mating type loci. FKH1 therefore performs a positive role in silencing at HMRa, whereas FKH2 plays a negative role (1). During mating type switching, information at the MAT locus is replaced by information contained at one of two silent loci, HML or HMR, through a regulated gene conversion event. In MATa strains, HML is the preferred donor, and this preference is dependent upon a cis-acting sequence called the recombination enhancer. FKH1 and the Swi4p/Swi6p containing SCB-binding factor (SBF) independently regulate donor preference through direct interactions with the recombination enhancer, with Fkh1p binding in the G2 phase and SBF binding in the G1 phase of the cell cycle (8). Deletion of FKH1 or mutation of the forkhead binding site in the enhancer reduces usage of the preferred donor and deletion of both FKH1 and SBF results in a nearly complete loss of preference for HML in MATa cells (5).

FKH1 is a member of a conserved forkhead (FOX) family of transcription factors that includes at least 43 members identified in humans, some of which have been implicated in cell cycle regulation (18, 19). Several parallels exist between one of these forkhead factors, FOXM1 (OMIM) and both FKH1 and FKH2. Similar to FKH1 and FKH2, the expression of FOXM1 is induced during the G1/S phase transition (20 and reviewed in 19). FOXM1 regulates the expression of a similar cluster of human genes during G2 and M phase and is required for the proper execution of mitosis and cytokinesis, as well as chromosome stability and the spindle checkpoint (reviewed in 21). The expression of FOXM1 is tightly correlated with cellular proliferative rate, is often elevated in human carcinomas and is actively involved in tumor development (reviewed in 21, 19).

Last updated: 2010-01-28 Contact SGD

References cited on this page View Complete Literature Guide for FKH1
1) Hollenhorst PC, et al.  (2000) Forkhead genes in transcriptional silencing, cell morphology and the cell cycle. Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae. Genetics 154(4):1533-48
2) Zhu G, et al.  (2000) Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth. Nature 406(6791):90-4
3) Kumar R, et al.  (2000) Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase. Curr Biol 10(15):896-906
4) Hollenhorst PC, et al.  (2001) Mechanisms controlling differential promoter-occupancy by the yeast forkhead proteins Fkh1p and Fkh2p: implications for regulating the cell cycle and differentiation. Genes Dev 15(18):2445-56
5) Sun K, et al.  (2002) Saccharomyces forkhead protein Fkh1 regulates donor preference during mating-type switching through the recombination enhancer. Genes Dev 16(16):2085-96
6) Morillon A, et al.  (2003) Regulation of elongating RNA polymerase II by forkhead transcription factors in yeast. Science 300(5618):492-5
7) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
8) Coic E, et al.  (2006) Cell cycle-dependent regulation of Saccharomyces cerevisiae donor preference during mating-type switching by SBF (Swi4/Swi6) and Fkh1. Mol Cell Biol 26(14):5470-80
9) Knott SR, et al.  (2012) Forkhead Transcription Factors Establish Origin Timing and Long-Range Clustering in S. cerevisiae. Cell 148(1-2):99-111
10) Li J, et al.  (2012) Regulation of Budding Yeast Mating-Type Switching Donor Preference by the FHA Domain of Fkh1. PLoS Genet 8(4):e1002630
11) Ghosh Dastidar R, et al.  (2012) The nuclear localization of SWI/SNF proteins is subjected to oxygen regulation. Cell Biosci 2(1):30
12) Jorgensen P and Tyers M  (2000) The fork'ed path to mitosis. Genome Biol 1(3):REVIEWS1022
13) Bahler J  (2005) Cell-cycle control of gene expression in budding and fission yeast. Annu Rev Genet 39:69-94
14) Spellman PT, et al.  (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9(12):3273-97
15) Pic A, et al.  (2000) The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF. EMBO J 19(14):3750-61
16) Koranda M, et al.  (2000) Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Nature 406(6791):94-8
17) Sherriff JA, et al.  (2007) The Isw2 chromatin-remodeling ATPase cooperates with the Fkh2 transcription factor to repress transcription of the B-type cyclin gene CLB2. Mol Cell Biol 27(8):2848-60
18) Katoh M and Katoh M  (2004) Human FOX gene family (Review). Int J Oncol 25(5):1495-500
19) Carlsson P and Mahlapuu M  (2002) Forkhead transcription factors: key players in development and metabolism. Dev Biol 250(1):1-23
20) Pramila T, et al.  (2006) The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle. Genes Dev 20(16):2266-78
21) Laoukili J, et al.  (2007) FoxM1: At the crossroads of ageing and cancer. Biochim Biophys Acta 1775(1):92-102
22) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104
23) Zhu C, et al.  (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556-66