CYC8/YBR112C Summary 
| Standard Name | CYC8 |
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| Systematic Name | YBR112C |
| Alias | CRT8 1 , SSN6 |
| Feature Type | ORF, Verified |
| Description | General transcriptional co-repressor, acts together with Tup1p; also acts as part of a transcriptional co-activator complex that recruits the SWI/SNF and SAGA complexes to promoters; can form the prion [OCT+] (2, 3, 4 and see Summary Paragraph) Also known as: [OCT1+] 4 , [OCT] |
| Name Description | CYtochrome C |
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| Note: this feature is encoded on the Crick strand. | |
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| Genetic position: 56 cM |
| 150 total interaction(s) for 100 unique genes/features. | |
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| Localization | |
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| Phosphorylation | PhosphoGRID | PhosphoPep Database |
| Structure | |
| Homologs |
| Note: this feature is encoded on the Crick strand. | |||||||||||||
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| Genetic position: 56 cM | |||||||||||||
| Last Update | Coordinates: 2011-02-03 | Sequence: 1997-01-28 | ||||||||||||
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| S288C only | |
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| S288C vs. other species | |
| S288C vs. other strains |
| External Links | All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB |
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| Primary SGDID | S000000316 |
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The Tup1p-Cyc8p corepressor is important for the repression of many genes involved in a wide variety of physiological processes (5, 2). Tup1p-Cyc8p may also be involved in the derepression of at least some target genes (6, 7). The active form of the corepressor consists of a protein complex containing four Tup1p subunits and a single Cyc8p subunit (8, 9). The Tup1 protein comprises three functionally defined domains: an N-terminus involved in the interaction with Cyc8p (10, 11, 12); a central domain required for the repression activity of the complex (13, 14); and a C-terminus containing seven WD40 repeats that form a beta-transducin-like propeller structure important for protein interactions and tetramerization (15).
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 (13, 16, 17). 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 (18, 19, 13). 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 (20, 21).
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 (22), Mig1p, which regulates glucose-repressed genes (23), Rfx1p, which is involved in DNA repair (24), and Sko1p, which is involved in stress responses (25). 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 (26). 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 (27).
Last updated: 2005-06-28 
| 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) | 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 |
| 3) | Proft M and Struhl K (2002) Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress. Mol Cell 9(6):1307-17 |
| 4) | Patel BK, et al. (2009) The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion. Nat Cell Biol 11(3):344-9 |
| 5) | Courey AJ and Jia S (2001) Transcriptional repression: the long and the short of it. Genes Dev 15(21):2786-96 |
| 6) | 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 |
| 7) | 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 |
| 8) | Redd MJ, et al. (1997) A complex composed of tup1 and ssn6 represses transcription in vitro. J Biol Chem 272(17):11193-7 |
| 9) | 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 |
| 10) | Carrico PM and Zitomer RS (1998) Mutational analysis of the Tup1 general repressor of yeast. Genetics 148(2):637-44 |
| 11) | 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 |
| 12) | 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 |
| 13) | 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 |
| 14) | Tzamarias D and Struhl K (1994) Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Nature 369(6483):758-61 |
| 15) | 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 |
| 16) | Watson AD, et al. (2000) Ssn6-Tup1 interacts with class I histone deacetylases required for repression. Genes Dev 14(21):2737-44 |
| 17) | 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 |
| 18) | Davie JK, et al. (2003) Tup1-Ssn6 interacts with multiple class I histone deacetylases in vivo. J Biol Chem 278(50):50158-62 |
| 19) | Davie JK, et al. (2002) Histone-dependent association of Tup1-Ssn6 with repressed genes in vivo. Mol Cell Biol 22(3):693-703 |
| 20) | 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 |
| 21) | 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 |
| 22) | 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 |
| 23) | 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 |
| 24) | 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 |
| 25) | 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 |
| 26) | Robyr D, et al. (2002) Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell 109(4):437-46 |
| 27) | 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 |
