TUP1/YCR084C Summary Help

Standard Name TUP1
Systematic Name YCR084C
Alias AAR1 , AER2 , AMM1 , CRT4 1 , CYC9 2 , 3 , FLK1 4 , ROX4 , SFL2 , UMR7 3
Feature Type ORF, Verified
Description General repressor of transcription, forms complex with Cyc8p, involved in the establishment of repressive chromatin structure through interactions with histones H3 and H4, appears to enhance expression of some genes (5, 6, 7, 8, 9, 10 and see Summary Paragraph)
Name Description deoxyThymidine monophosphate UPtake
Chromosomal Location
ChrIII:262452 to 260311 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 77 cM
Gene Ontology Annotations All TUP1 GO evidence and references
  View Computational GO annotations for TUP1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulatory Role
Regulatory modules predicted: stressResponse (397)
Mutant phenotypes All TUP1 Phenotype evidence and references
Classical genetics
dominant negative
null
Large-scale survey
null
Resources
interactions All TUP1 Interaction evidence and references
149 total interaction(s) for 90 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 18
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 28
  • Co-crystal Structure: 1
  • Co-fractionation: 2
  • Co-localization: 2
  • PCA: 8
  • Protein-peptide: 1
  • Reconstituted Complex: 19
  • Two-hybrid: 38
Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 3
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 9
  • Synthetic Growth Defect: 5
  • Synthetic Lethality: 1
  • Synthetic Rescue: 10
Resources
Expression Summary
histogram
Resources
Protein Information All TUP1 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIII:262452 to 260311 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 77 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..2142 262452..260311 2011-02-03 1997-01-28
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 SGDIDS000000680
SUMMARY PARAGRAPH for TUP1

The Tup1p-Cyc8p corepressor is important for the repression of many genes involved in a wide variety of physiological processes (11, 12). Tup1p-Cyc8p may also be involved in the derepression of at least some target genes (13, 14). The active form of the corepressor consists of a protein complex containing four Tup1p subunits and a single Cyc8p subunit (15, 16). The Tup1 protein comprises three functionally defined domains: an N-terminus involved in the interaction with Cyc8p (17, 18, 19); a central domain required for the repression activity of the complex (5, 20); and a C-terminus containing seven WD40 repeats that form a beta-transducin-like propeller structure important for protein interactions and tetramerization (21).

Tup1p-Cyc8p mediates repression of target genes by different molecular mechanisms. Tup1p-Cyc8p can recruit histone deacetylases to genes, which results in deacetylation of histones producing a repressive chromatin structure (5, 22, 23). Tup1p-Cyc8p can also interact with hypoacetylated N-terminal tails of histones H3 (Hht1p and Hht2p) and H4 (Hhf1p and Hhf2p) that have been programmed for repression by the action of histone deacetylases (24, 25, 5). In addition, Tup1p-Cyc8p can interfere directly with the transcriptional machinery by interacting with factors important for the repressive activity of the RNA polymerase II mediator subcomplex (26, 27).

Tup1p-Cyc8p is recruited to target genes by interaction with DNA-bound transcriptional repressors that recognize specific sequences within the target gene promoters. Such repressors include MatAlpha2p, which regulates mating-type-specific genes (28), Mig1p, which regulates glucose-repressed genes (29), Rfx1p, which is involved in DNA repair (30), and Sko1p, which is involved in stress responses (31). This gene-specific role has been complemented by observations that Tup1p might be involved in establishing domains of heterochromatin structure in the subtelomeric regions of chromosomes (32). These "HAST" domains contain clusters of Tup1p- and Cyc8p-repressed genes and coincide with regions that are deacetylated by the histone deacetylase Hda1p. Therefore, Tup1p-Cyc8p may establish the formation of heterochromatin in these regions by recruiting Hda1p. HAST domains are distinct from adjacent heterochromatin regions that are established via Tup1p-independent recruitment of the Sir2p histone deacetylase (33).

Last updated: 2005-06-28

References cited on this page View Complete Literature Guide for TUP1
1) Zhou Z and Elledge SJ  (1992) Isolation of crt mutants constitutive for transcription of the DNA damage inducible gene RNR3 in Saccharomyces cerevisiae. Genetics 131(4):851-66
2) Rothstein RJ and Sherman F  (1980) Genes affecting the expression of cytochrome c in yeast: genetic mapping and genetic interactions. Genetics 94(4):871-89
3) Lemontt JF, et al.  (1980) Pleiotropic Mutations at the TUP1 Locus That Affect the Expression of Mating-Type-Dependent Functions in SACCHAROMYCES CEREVISIAE. Genetics 94(4):899-920
4) Stark HC, et al.  (1980) Pleiotropic properties of a yeast mutant insensitive to catabolite repression. Genetics 94(4):921-8
5) Edmondson DG, et al.  (1996) Repression domain of the yeast global repressor Tup1 interacts directly with histones H3 and H4. Genes Dev 10(10):1247-59
6) Cooper JP, et al.  (1994) The global transcriptional regulators, SSN6 and TUP1, play distinct roles in the establishment of a repressive chromatin structure. Genes Dev 8(12):1400-10
7) Williams FE, et al.  (1991) The CYC8 and TUP1 proteins involved in glucose repression in Saccharomyces cerevisiae are associated in a protein complex. Mol Cell Biol 11(6):3307-16
8) Zhang L and Guarente L  (1994) Evidence that TUP1/SSN6 has a positive effect on the activity of the yeast activator HAP1. Genetics 136(3):813-7
9) Keleher CA, et al.  (1992) Ssn6-Tup1 is a general repressor of transcription in yeast. Cell 68(4):709-19
10) Conlan RS, et al.  (1999) The Tup1-Cyc8 protein complex can shift from a transcriptional co-repressor to a transcriptional co-activator. J Biol Chem 274(1):205-10
11) Courey AJ and Jia S  (2001) Transcriptional repression: the long and the short of it. Genes Dev 15(21):2786-96
12) Smith RL and Johnson AD  (2000) Turning genes off by Ssn6-Tup1: a conserved system of transcriptional repression in eukaryotes. Trends Biochem Sci 25(7):325-30
13) Mennella TA, et al.  (2003) Recruitment of Tup1-Ssn6 by yeast hypoxic genes and chromatin-independent exclusion of TATA binding protein. Eukaryot Cell 2(6):1288-303
14) Papamichos-Chronakis M, et al.  (2002) Cti6, a PHD domain protein, bridges the Cyc8-Tup1 corepressor and the SAGA coactivator to overcome repression at GAL1. Mol Cell 9(6):1297-305
15) Redd MJ, et al.  (1997) A complex composed of tup1 and ssn6 represses transcription in vitro. J Biol Chem 272(17):11193-7
16) Varanasi US, et al.  (1996) The Cyc8 (Ssn6)-Tup1 corepressor complex is composed of one Cyc8 and four Tup1 subunits. Mol Cell Biol 16(12):6707-14
17) Carrico PM and Zitomer RS  (1998) Mutational analysis of the Tup1 general repressor of yeast. Genetics 148(2):637-44
18) Zhang Z, et al.  (2002) Mutations of the WD repeats that compromise Tup1 repression function maintain structural integrity of the WD domain trypsin-resistant core. Arch Biochem Biophys 406(1):47-54
19) Zhang Z, et al.  (2002) Functional dissection of the global repressor Tup1 in yeast: dominant role of the C-terminal repression domain. Genetics 161(3):957-69
20) Tzamarias D and Struhl K  (1994) Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Nature 369(6483):758-61
21) Sprague ER, et al.  (2000) Structure of the C-terminal domain of Tup1, a corepressor of transcription in yeast. EMBO J 19(12):3016-27
22) Watson AD, et al.  (2000) Ssn6-Tup1 interacts with class I histone deacetylases required for repression. Genes Dev 14(21):2737-44
23) Wu J, et al.  (2001) TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity in yeast. Mol Cell 7(1):117-26
24) Davie JK, et al.  (2003) Tup1-Ssn6 interacts with multiple class I histone deacetylases in vivo. J Biol Chem 278(50):50158-62
25) Davie JK, et al.  (2002) Histone-dependent association of Tup1-Ssn6 with repressed genes in vivo. Mol Cell Biol 22(3):693-703
26) Lee M, et al.  (2000) Genetic analysis of the role of Pol II holoenzyme components in repression by the Cyc8-Tup1 corepressor in yeast. Genetics 155(4):1535-42
27) Papamichos-Chronakis M, et al.  (2000) Hrs1/Med3 is a Cyc8-Tup1 corepressor target in the RNA polymerase II holoenzyme. J Biol Chem 275(12):8397-403
28) Komachi K and Johnson AD  (1997) Residues in the WD repeats of Tup1 required for interaction with alpha2. Mol Cell Biol 17(10):6023-8
29) Treitel MA and Carlson M  (1995) Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein. Proc Natl Acad Sci U S A 92(8):3132-6
30) Huang M, et al.  (1998) The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Cell 94(5):595-605
31) Proft M, et al.  (2001) Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in response to osmotic stress. EMBO J 20(5):1123-33
32) Robyr D, et al.  (2002) Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell 109(4):437-46
33) Fagerstrom-Billai F and Wright AP  (2005) Functional comparison of the Tup11 and Tup12 transcriptional corepressors in fission yeast. Mol Cell Biol 25(2):716-27