9efw

Structural highlights

Function

FKH1_YEAST Transcription factor that regulates the expression of the CLB2 cluster of genes during the G2/M phase of the mitotic cell cycle (PubMed:10894548, PubMed:10894549, PubMed:10959837, PubMed:11562353, PubMed:12702877, PubMed:17283050, PubMed:24504085). 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 (PubMed:10894548, PubMed:10959837, PubMed:11562353). Involved in HMRa silencing (PubMed:10747051). FKH1 and FKH2 associate with the coding regions of active genes and influence, in opposing ways, transcriptional elongation and termination, and coordinate early transcription elongation and pre-mRNA processing (PubMed:12702877). Both FKH1 and FKH2 play a role as regulators of lifespan in collaboration with the anaphase-promoting complex (APC), likely through combined regulation of stress response, genomic stability, and cell cycle regulation (PubMed:22438832). FKH1 and FKH2 function also in controlling yeast cell morphology by preventing preudohyphal growth (PubMed:10747051, PubMed:10894548). Acts as a rate-limiting replication origin activator via its interaction with the origin recognition complex (ORC) (PubMed:22265405, PubMed:26728715). Plays a transcription-independent role in recombination donor preference during mating-type switching through binding to the recombination enhancer (RE), a 700-bp cis-acting element that controls recombination along the left arm of chromosome III (PubMed:12183363, PubMed:16809780, PubMed:22496671, PubMed:27257873).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]}

References

1. ↑ Hollenhorst PC, Bose ME, Mielke MR, Müller U, Fox CA. Forkhead genes in transcriptional silencing, cell morphology and the cell cycle. Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae. Genetics. 2000 Apr;154(4):1533-48. PMID:10747051 doi:10.1093/genetics/154.4.1533
2. ↑ Zhu G, Spellman PT, Volpe T, Brown PO, Botstein D, Davis TN, Futcher B. Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth. Nature. 2000 Jul 6;406(6791):90-4. PMID:10894548 doi:10.1038/35017581
3. ↑ Koranda M, Schleiffer A, Endler L, Ammerer G. Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Nature. 2000 Jul 6;406(6791):94-8. PMID:10894549 doi:10.1038/35017589
4. ↑ Kumar R, Reynolds DM, Shevchenko A, Shevchenko A, Goldstone SD, Dalton S. Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase. Curr Biol. 2000 Jul 27-Aug 10;10(15):896-906. PMID:10959837 doi:10.1016/s0960-9822(00)00618-7
5. ↑ Hollenhorst PC, Pietz G, Fox CA. Mechanisms controlling differential promoter-occupancy by the yeast forkhead proteins Fkh1p and Fkh2p: implications for regulating the cell cycle and differentiation. Genes Dev. 2001 Sep 15;15(18):2445-56. PMID:11562353 doi:10.1101/gad.906201
6. ↑ Sun K, Coïc E, Zhou Z, Durrens P, Haber JE. Saccharomyces forkhead protein Fkh1 regulates donor preference during mating-type switching through the recombination enhancer. Genes Dev. 2002 Aug 15;16(16):2085-96. PMID:12183363 doi:10.1101/gad.994902
7. ↑ Morillon A, O'Sullivan J, Azad A, Proudfoot N, Mellor J. Regulation of elongating RNA polymerase II by forkhead transcription factors in yeast. Science. 2003 Apr 18;300(5618):492-5. PMID:12702877 doi:10.1126/science.1081379
8. ↑ Coïc E, Sun K, Wu C, Haber JE. Cell cycle-dependent regulation of Saccharomyces cerevisiae donor preference during mating-type switching by SBF (Swi4/Swi6) and Fkh1. Mol Cell Biol. 2006 Jul;26(14):5470-80. PMID:16809780 doi:10.1128/MCB.02443-05
9. ↑ Sherriff JA, Kent NA, Mellor J. The Isw2 chromatin-remodeling ATPase cooperates with the Fkh2 transcription factor to repress transcription of the B-type cyclin gene CLB2. Mol Cell Biol. 2007 Apr;27(8):2848-60. PMID:17283050 doi:10.1128/MCB.01798-06
10. ↑ Knott SR, Peace JM, Ostrow AZ, Gan Y, Rex AE, Viggiani CJ, Tavaré S, Aparicio OM. Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Cell. 2012 Jan 20;148(1-2):99-111. PMID:22265405 doi:10.1016/j.cell.2011.12.012
11. ↑ Postnikoff SD, Malo ME, Wong B, Harkness TA. The yeast forkhead transcription factors fkh1 and fkh2 regulate lifespan and stress response together with the anaphase-promoting complex. PLoS Genet. 2012;8(3):e1002583. PMID:22438832 doi:10.1371/journal.pgen.1002583
12. ↑ Li J, Coïc E, Lee K, Lee CS, Kim JA, Wu Q, Haber JE. Regulation of budding yeast mating-type switching donor preference by the FHA domain of Fkh1. PLoS Genet. 2012;8(4):e1002630. PMID:22496671 doi:10.1371/journal.pgen.1002630
13. ↑ Ostrow AZ, Nellimoottil T, Knott SR, Fox CA, Tavaré S, Aparicio OM. Fkh1 and Fkh2 bind multiple chromosomal elements in the S. cerevisiae genome with distinct specificities and cell cycle dynamics. PLoS One. 2014 Feb 4;9(2):e87647. PMID:24504085 doi:10.1371/journal.pone.0087647
14. ↑ Peace JM, Villwock SK, Zeytounian JL, Gan Y, Aparicio OM. Quantitative BrdU immunoprecipitation method demonstrates that Fkh1 and Fkh2 are rate-limiting activators of replication origins that reprogram replication timing in G1 phase. Genome Res. 2016 Mar;26(3):365-75. PMID:26728715 doi:10.1101/gr.196857.115
15. ↑ Dummer AM, Su Z, Cherney R, Choi K, Denu J, Zhao X, Fox CA. Binding of the Fkh1 Forkhead Associated Domain to a Phosphopeptide within the Mph1 DNA Helicase Regulates Mating-Type Switching in Budding Yeast. PLoS Genet. 2016 Jun 3;12(6):e1006094. PMID:27257873 doi:10.1371/journal.pgen.1006094