Forkhead genes in transcriptional silencing, cell morphology and the cell cycle

Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae

Peter Hollenhorst, Melissa E. Bose, Melissa R. Mielke, Ulrika Müller, Catherine A. Fox

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The SIR1 gene is one of four specialized genes in Saccharomyces cerevisiae required for repressing transcription at the silent mating-type cassettes, HMLα and HMRa, by a mechanism known as silencing. Silencing requires the assembly of a specialized chromatin structure analogous to heterochromatin. FKH1 was isolated as a gene that, when expressed in multiple copies, could substitute for the function of SIR1 in silencing HMRa. FKH1 (Forkhead Homologue One) was named for its homology to the forkhead family of eukaryotic transcription factors classified on the basis of a conserved DNA binding domain. Deletion of FKH1 caused a defect in silencing HMRa, indicating that FKH1 has a positive role in silencing. Significantly, deletion of both FKH1 and its closest homologue in yeast, FKH2, caused a form of yeast pseudohyphal growth, indicating that the two genes have redundant functions in controlling yeast cell morphology. By several criteria, fkh1Δ fkh2Δ-induced pseudohyphal growth was distinct from the nutritionally induced form of pseudohyphal growth observed in some strains of S. cerevisiae. Although FKH2 is redundant with FKH1 in controlling pseudohyphal growth, the two genes have different functions in silencing HMRa. High-copy expression of CLB2, a G2/M-phase cyclin, prevented fkh1Δ fkh2Δ-induced pseudohyphal growth and modulated some of the fkhΔ-induced silencing phenotypes. Interestingly, deletions in either FKH1 or FKH2 alone caused subtle but opposite effects on cell-cycle progression and CLB2 mRNA expression, consistent with a role for each of these genes in modulating the cell cycle and having opposing effects on silencing. The differences between Fkh1p and Fkh2p in vivo were not attributable to differences in their DNA binding domains.

Original languageEnglish (US)
Pages (from-to)1533-1548
Number of pages16
JournalGenetics
Volume154
Issue number4
StatePublished - Apr 2000
Externally publishedYes

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Saccharomyces cerevisiae
Cell Cycle
Genes
Growth
Yeasts
Cyclins
Heterochromatin
G2 Phase
DNA
Cell Division
Chromatin
Transcription Factors
Phenotype
Messenger RNA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Forkhead genes in transcriptional silencing, cell morphology and the cell cycle : Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae. / Hollenhorst, Peter; Bose, Melissa E.; Mielke, Melissa R.; Müller, Ulrika; Fox, Catherine A.

In: Genetics, Vol. 154, No. 4, 04.2000, p. 1533-1548.

Research output: Contribution to journalArticle

Hollenhorst, Peter ; Bose, Melissa E. ; Mielke, Melissa R. ; Müller, Ulrika ; Fox, Catherine A. / Forkhead genes in transcriptional silencing, cell morphology and the cell cycle : Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae. In: Genetics. 2000 ; Vol. 154, No. 4. pp. 1533-1548.
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