Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1999 Jan 1;337(Pt 1):13–17.

Groucho/transducin-like enhancer of split (TLE) family members interact with the yeast transcriptional co-repressor SSN6 and mammalian SSN6-related proteins: implications for evolutionary conservation of transcription repression mechanisms.

D Grbavec 1, R Lo 1, Y Liu 1, A Greenfield 1, S Stifani 1
PMCID: PMC1219929  PMID: 9854018

Abstract

The yeast proteins TUP1 and SSN6 form a transcription repressor complex that is recruited to different promoters via pathway-specific DNA-binding proteins and regulates the expression of a variety of genes. TUP1 is functionally related to invertebrate and vertebrate transcriptional repressors of the Groucho/transducin-like Enhancer of split (TLE) family. The aim was to examine whether similar mechanisms underlie the transcription repression functions of TUP1 and Groucho/TLEs by determining whether TLE family members can interact with yeast SSN6 and mammalian SSN6-like proteins. It is shown in the present work that SSN6 binds to TLE1 and mediates transcriptional repression when expressed in mammalian cells. Moreover, TLE1 and TLE2 interact with two mammalian proteins related to SSN6, designated as the products of the ubiquitously transcribed tetratricopeptide-repeat genes on the Y (or X) chromosomes (UTY/X). These findings suggest that mammalian TLE and UTY/X proteins may mediate repression mechanisms similar to those performed by TUP1-SSN6 in yeast.

Full Text

The Full Text of this article is available as a PDF (167.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Dubnicoff T., Valentine S. A., Chen G., Shi T., Lengyel J. A., Paroush Z., Courey A. J. Conversion of dorsal from an activator to a repressor by the global corepressor Groucho. Genes Dev. 1997 Nov 15;11(22):2952–2957. doi: 10.1101/gad.11.22.2952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Edmondson D. G., Smith M. M., Roth S. Y. Repression domain of the yeast global repressor Tup1 interacts directly with histones H3 and H4. Genes Dev. 1996 May 15;10(10):1247–1259. doi: 10.1101/gad.10.10.1247. [DOI] [PubMed] [Google Scholar]
  3. Fisher A. L., Ohsako S., Caudy M. The WRPW motif of the hairy-related basic helix-loop-helix repressor proteins acts as a 4-amino-acid transcription repression and protein-protein interaction domain. Mol Cell Biol. 1996 Jun;16(6):2670–2677. doi: 10.1128/mcb.16.6.2670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Friesen H., Hepworth S. R., Segall J. An Ssn6-Tup1-dependent negative regulatory element controls sporulation-specific expression of DIT1 and DIT2 in Saccharomyces cerevisiae. Mol Cell Biol. 1997 Jan;17(1):123–134. doi: 10.1128/mcb.17.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goebl M., Yanagida M. The TPR snap helix: a novel protein repeat motif from mitosis to transcription. Trends Biochem Sci. 1991 May;16(5):173–177. doi: 10.1016/0968-0004(91)90070-c. [DOI] [PubMed] [Google Scholar]
  6. Grbavec D., Stifani S. Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif. Biochem Biophys Res Commun. 1996 Jun 25;223(3):701–705. doi: 10.1006/bbrc.1996.0959. [DOI] [PubMed] [Google Scholar]
  7. Greenfield A., Carrel L., Pennisi D., Philippe C., Quaderi N., Siggers P., Steiner K., Tam P. P., Monaco A. P., Willard H. F. The UTX gene escapes X inactivation in mice and humans. Hum Mol Genet. 1998 Apr;7(4):737–742. doi: 10.1093/hmg/7.4.737. [DOI] [PubMed] [Google Scholar]
  8. Greenfield A., Scott D., Pennisi D., Ehrmann I., Ellis P., Cooper L., Simpson E., Koopman P. An H-YDb epitope is encoded by a novel mouse Y chromosome gene. Nat Genet. 1996 Dec;14(4):474–478. doi: 10.1038/ng1296-474. [DOI] [PubMed] [Google Scholar]
  9. Hartley D. A., Preiss A., Artavanis-Tsakonas S. A deduced gene product from the Drosophila neurogenic locus, enhancer of split, shows homology to mammalian G-protein beta subunit. Cell. 1988 Dec 2;55(5):785–795. doi: 10.1016/0092-8674(88)90134-1. [DOI] [PubMed] [Google Scholar]
  10. Husain J., Lo R., Grbavec D., Stifani S. Affinity for the nuclear compartment and expression during cell differentiation implicate phosphorylated Groucho/TLE1 forms of higher molecular mass in nuclear functions. Biochem J. 1996 Jul 15;317(Pt 2):523–531. doi: 10.1042/bj3170523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jiménez G., Paroush Z., Ish-Horowicz D. Groucho acts as a corepressor for a subset of negative regulators, including Hairy and Engrailed. Genes Dev. 1997 Nov 15;11(22):3072–3082. doi: 10.1101/gad.11.22.3072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Keleher C. A., Redd M. J., Schultz J., Carlson M., Johnson A. D. Ssn6-Tup1 is a general repressor of transcription in yeast. Cell. 1992 Feb 21;68(4):709–719. doi: 10.1016/0092-8674(92)90146-4. [DOI] [PubMed] [Google Scholar]
  13. Komachi K., Redd M. J., Johnson A. D. The WD repeats of Tup1 interact with the homeo domain protein alpha 2. Genes Dev. 1994 Dec 1;8(23):2857–2867. doi: 10.1101/gad.8.23.2857. [DOI] [PubMed] [Google Scholar]
  14. Koop K. E., MacDonald L. M., Lobe C. G. Transcripts of Grg4, a murine groucho-related gene, are detected in adjacent tissues to other murine neurogenic gene homologues during embryonic development. Mech Dev. 1996 Sep;59(1):73–87. doi: 10.1016/0925-4773(96)00582-5. [DOI] [PubMed] [Google Scholar]
  15. Lahn B. T., Page D. C. Functional coherence of the human Y chromosome. Science. 1997 Oct 24;278(5338):675–680. doi: 10.1126/science.278.5338.675. [DOI] [PubMed] [Google Scholar]
  16. Mazeyrat S., Saut N., Sargent C. A., Grimmond S., Longepied G., Ehrmann I. E., Ellis P. S., Greenfield A., Affara N. A., Mitchell M. J. The mouse Y chromosome interval necessary for spermatogonial proliferation is gene dense with syntenic homology to the human AZFa region. Hum Mol Genet. 1998 Oct;7(11):1713–1724. doi: 10.1093/hmg/7.11.1713. [DOI] [PubMed] [Google Scholar]
  17. Miyasaka H., Choudhury B. K., Hou E. W., Li S. S. Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein. Eur J Biochem. 1993 Aug 15;216(1):343–352. doi: 10.1111/j.1432-1033.1993.tb18151.x. [DOI] [PubMed] [Google Scholar]
  18. Palaparti A., Baratz A., Stifani S. The Groucho/transducin-like enhancer of split transcriptional repressors interact with the genetically defined amino-terminal silencing domain of histone H3. J Biol Chem. 1997 Oct 17;272(42):26604–26610. doi: 10.1074/jbc.272.42.26604. [DOI] [PubMed] [Google Scholar]
  19. Paroush Z., Finley R. L., Jr, Kidd T., Wainwright S. M., Ingham P. W., Brent R., Ish-Horowicz D. Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins. Cell. 1994 Dec 2;79(5):805–815. doi: 10.1016/0092-8674(94)90070-1. [DOI] [PubMed] [Google Scholar]
  20. Pinto M., Lobe C. G. Products of the grg (Groucho-related gene) family can dimerize through the amino-terminal Q domain. J Biol Chem. 1996 Dec 20;271(51):33026–33031. doi: 10.1074/jbc.271.51.33026. [DOI] [PubMed] [Google Scholar]
  21. Redd M. J., Stark M. R., Johnson A. D. Accessibility of alpha 2-repressed promoters to the activator Gal4. Mol Cell Biol. 1996 Jun;16(6):2865–2869. doi: 10.1128/mcb.16.6.2865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schultz J., Marshall-Carlson L., Carlson M. The N-terminal TPR region is the functional domain of SSN6, a nuclear phosphoprotein of Saccharomyces cerevisiae. Mol Cell Biol. 1990 Sep;10(9):4744–4756. doi: 10.1128/mcb.10.9.4744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith R. L., Redd M. J., Johnson A. D. The tetratricopeptide repeats of Ssn6 interact with the homeo domain of alpha 2. Genes Dev. 1995 Dec 1;9(23):2903–2910. doi: 10.1101/gad.9.23.2903. [DOI] [PubMed] [Google Scholar]
  24. Stifani S., Blaumueller C. M., Redhead N. J., Hill R. E., Artavanis-Tsakonas S. Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins. Nat Genet. 1992 Oct;2(2):119–127. doi: 10.1038/ng1092-119. [DOI] [PubMed] [Google Scholar]
  25. Thirunavukkarasu K., Mahajan M., McLarren K. W., Stifani S., Karsenty G. Two domains unique to osteoblast-specific transcription factor Osf2/Cbfa1 contribute to its transactivation function and its inability to heterodimerize with Cbfbeta. Mol Cell Biol. 1998 Jul;18(7):4197–4208. doi: 10.1128/mcb.18.7.4197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tzamarias D., Struhl K. Distinct TPR motifs of Cyc8 are involved in recruiting the Cyc8-Tup1 corepressor complex to differentially regulated promoters. Genes Dev. 1995 Apr 1;9(7):821–831. doi: 10.1101/gad.9.7.821. [DOI] [PubMed] [Google Scholar]
  27. Tzamarias D., Struhl K. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Nature. 1994 Jun 30;369(6483):758–761. doi: 10.1038/369758a0. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES