FHL1/YPR104C Summary Help

Standard Name FHL1 1
Systematic Name YPR104C
Alias SPP42 2 , 3
Feature Type ORF, Verified
Description Regulator of ribosomal protein (RP) transcription; has forkhead associated domain that binds phosphorylated proteins; recruits coactivator Ifh1p or corepressor Crf1p to RP gene promoters; also has forkhead DNA-binding domain though in vitro DNA binding assays give inconsistent results; computational analyses suggest it binds DNA directly at highly active RP genes and indirectly through Rap1p motifs at others; suppresses RNA pol III and splicing factor prp4 mutants (1, 2, 4, 5, 6, 7, 8, 9 and see Summary Paragraph)
Name Description Fork Head-Like 1
Chromosomal Location
ChrXVI:736433 to 733623 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All FHL1 GO evidence and references
  View Computational GO annotations for FHL1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 365 genes
Regulators 3 genes
Resources
Classical genetics
conditional
null
overexpression
Large-scale survey
null
reduction of function
Resources
54 total interaction(s) for 42 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 10
  • Affinity Capture-Western: 9
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 8
  • Negative Genetic: 1
  • Positive Genetic: 15
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 2
  • Synthetic Rescue: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 936
Molecular Weight (Da) 103,501
Isoelectric Point (pI) 5.7
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXVI:736433 to 733623 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2811 736433..733623 2011-02-03 1996-07-31
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 SGDIDS000006308
SUMMARY PARAGRAPH for FHL1

Originally isolated as a suppressor of an RNA polymerase III mutation and independently as a supressor of a splicing mutation, FHL1 encodes a protein that is involved in regulation of the expression of ribosomal protein (RP) genes by RNA polymerase II (1, 2, 10, and reviewed in 8). Fhl1p has sequence similarity to the forkhead (FH), or "winged helix", domain generally considered to be a DNA binding domain (11, 1). However in vitro studies testing for direct DNA binding by Fhl1p have produced inconsistent results (5, 6, 7), and the FH domain can be deleted with almost no effect on cells (5). In constrast, deletion of the forkhead-associated (FHA) domain, which is involved in binding to phosphorylated threonine residues within proteins (12) and required for the interaction of Fhl1p with either Ifh1p or Crf1p (4), is nearly as deleterious as deletion of the entire FHL1 gene (5). Null mutations of FHL1 result in a severely reduced growth rate with cells having only 20% the normal amount of RNA and able to synthesize ribosomes at 5-10% the rate of wild-type cells (1, 5).

RP gene transcription is coordinated with that of rDNA transcription and is regulated in response to stress and growth conditions through a complex mechanism that involves Fhl1p, the coactivator Ifh1p, the corepressor Crf1p, and the TOR pathway (4). Fhl1p localizes to promoters of RP genes, where it can recruit either the activator protein Ifh1p or the repressor protein Crf1p (4, 11). Both Fhl1p and Ifh1p are localized to the nucleus all the time, but the localization of the repressor Crf1p is regulated by its phosphorylation state via the TOR pathway (4). Fhl1p localization to RP gene promoters and RP gene expression are dependent on Rap1p and Hmo1p (13, 14), however the phenotypes of both hmo1 and fhl1 nulls suggest that there is an additional pathway that regulates RP gene transcription (5, 14). Fhl1p is also loosely associated with the CURI complex, which is thought to repress transcription of ribosomal protein genes by sequestering the coactivator Ifh1p (15). Both the CURI complex and Hmo1p, which is required for rDNA transcription by RNA polymerase I, are thought to be involved in coordinate regulation of rDNA transcription and RP gene transcription to control production of ribosomes in response to growth conditions (reviewed in 8).

Founded by the forkhead homeotic gene of the fruit fly D. melanogaster, the forkhead family of proteins (FOX) contain the characteristic Fork Head (FH) domain and are widespread in eukaryotes, found throughout animals and fungi (16). The forkhead domains of animal and fungal sequences can be classified into a number of orthologous groups, with the members of the fungal groups being more similar to each other than to forkhead proteins from animals (16). Of the three groups found in fungi, S. cerevisiae has members in two of the groups: FKH1 and FKH2 in the Fox1 group and FHL1 in the Fox3 group (16). Many forkhead proteins have a second domain referred to as the Fork Head Associated (FHA) domain, though this domain is also found in other protein families and in plants and prokaryotes (12). The S. cerevisiae Fhl1 protein is similar to the FHA-domain containing proteins Fhl1 from S. pombe (17) and NtFHA1 from tobacco which can complement a fhl1 null mutation (18).

Last updated: 2010-02-12 Contact SGD

References cited on this page View Complete Literature Guide for FHL1
1) Hermann-Le Denmat S, et al.  (1994) Suppression of yeast RNA polymerase III mutations by FHL1, a gene coding for a fork head protein involved in rRNA processing. Mol Cell Biol 14(5):2905-13
2) Maddock JR, et al.  (1994) Extragenic suppressors of Saccharomyces cerevisiae prp4 mutations identify a negative regulator of PRP genes. Genetics 136(3):833-47
3) Maddock J  (1990) Genetic interactions among yeast gene products required for messenger RNA processing. Ph.D. thesis, Carnegie Mellon University, United States
4) Martin DE, et al.  (2004) TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell 119(7):969-79
5) Rudra D, et al.  (2005) Central role of Ifh1p-Fhl1p interaction in the synthesis of yeast ribosomal proteins. EMBO J 24(3):533-42
6) Badis G, et al.  (2008) A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell 32(6):878-87
7) Zhu C, et al.  (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556-66
8) Xiao L and Grove A  (2009) Coordination of Ribosomal Protein and Ribosomal RNA Gene Expression in Response to TOR Signaling. Curr Genomics 10(3):198-205
9) Zeevi D, et al.  (2011) Compensation for differences in gene copy number among yeast ribosomal proteins is encoded within their promoters. Genome Res 21(12):2114-28
10) Schawalder SB, et al.  (2004) Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1. Nature 432(7020):1058-61
11) Wade JT, et al.  (2004) The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes. Nature 432(7020):1054-8
12) Durocher D and Jackson SP  (2002) The FHA domain. FEBS Lett 513(1):58-66
13) Zhao Y, et al.  (2006) Fine-structure analysis of ribosomal protein gene transcription. Mol Cell Biol 26(13):4853-62
14) Hall DB, et al.  (2006) An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes and throughout the rRNA gene locus in Saccharomyces cerevisiae. Mol Cell Biol 26(9):3672-9
15) Rudra D, et al.  (2007) Potential interface between ribosomal protein production and pre-rRNA processing. Mol Cell Biol 27(13):4815-24
16) Wang M, et al.  (2009) Evolutionary selection pressure of forkhead domain and functional divergence. Gene 432(1-2):19-25
17) Szilagyi Z, et al.  (2005) Characterisation of two novel fork-head gene homologues of Schizosaccharomyces pombe: their involvement in cell cycle and sexual differentiation. Gene 348():101-9
18) Kim M, et al.  (2002) Forkhead-associated domains of the tobacco NtFHA1 transcription activator and the yeast Fhl1 forkhead transcription factor are functionally conserved. J Biol Chem 277(41):38781-90
19) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104