Abstract
The DNA-binding protein Rap1p fulfills many different functions in the yeast cell. It targets 5% of the promoters, acting both as a transcriptional activator and as a repressor, depending on the DNA sequence context. In addition, Rap1p is an essential structural component of yeast telomeres, where it contributes to telomeric silencing. Here we review the evidence indicating that Rap1p function is modulated by the precise architecture of the its binding site and its surroundings: long tracts of telomeric repeats for telomeric functions, specific sequences and orientation for maximal transcriptional activation, and specific DNA recognition sequences for complementary factors in other cases. Many of these functions are probably related to chromatin organization around Rap1p DNA binding sites, resulting from the very tight binding of Rap1p to DNA. We propose that Rap1p alters its structure to bind to different versions of its DNA binding sequence. These structural changes may modulate the function of Rap1p domains, providing different interacting surfaces for binding to specific co-operating factors, and thus contributing to the diversity of Rap1p function.
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References
Aronson B, Fisher AL, Blechman K, Caudy M, Gergen J (1997) Groucho-dependent and -independent repression activities of Runt domain proteins. Mol Cell Biol 17:5581–5587
Bi X, Broach JR (1999) UASrpg can function as a heterochromatin boundary element in yeast. Genes Dev 13:1089–1101
Boscheron C, Maillet L, Marcand S, Tsai-Pflugfelder M, Gasser SM, Gilson E (1996) Cooperation at a distance between silencers and proto-silencers at the yeast HML locus. EMBO J 15:2184–2195
Branden C, Tooze J (1999) Introduction to protein structure (2nd edn). Garland Publishing, New York
Carmen AA, Milne L, Grunstein M (2002) Acetylation of the yeast histone H4 N-terminus regulates its binding to heterochromatin protein SIR3. J Biol Chem 277:4778–4781
Cooper J (2000) Telomere transitions in yeast: the end of the chromosome as we know it. Curr Opin Genet Dev 10:169–177
De Sanctis V, La Terra S, Bianchi A, Shore D, Burderi L, Di Mauro E, Negri R (2002) In vivo topography of Rap1p-DNA complex at Saccharomyces cerevisiae TEF2UAS(RPG) during transcriptional regulation. J Mol Biol 318:333–349
Devlin C, Tice-Baldwin K, Shore D, Arndt KT (1991) RAP1 is required for BAS1/ BAS2 - and GCN4-dependent transcription of the yeast HIS4 gene. Mol Cell Biol 11:3642–3651
Drazinic CM, Smerage JB, López MC, Baker HV (1996) Activation mechanism of the multifunctional transcription factor repressor-activator protein 1 (Rap1p). Mol Cell Biol 16:3187–3196
Dubnicoff T, Valentine S, Chen G, Shi T, Lengyel J, Paroush Z, Courey A (1997) Conversion of Dorsal from activator to repressor by the global corepressor Groucho. Genes Dev 11:2952–2957
Fernandes L, Rodrigues-Pousada C, Struhl K (1997) Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae. Mol Cell Biol 17:6982–6993
Freeman K, Gwadz M, Shore D (1995) Molecular and genetic analysis of the toxic effect of RAP1 overexpression in yeast. Genetics 141:1253–1262
Gartenberg M (2000) The Sir proteins of Saccharomyces cerevisiae: mediators of transcriptional silencing and much more. Curr Opin Microbiol 3:132–137
Giesman D, Best L, Tatchell K (1991) The role of RAP1in the regulation of the MAT alpha locus. Mol Cell Biol 11:1069–1079
Gonçalves P, Maurer K, van Nieuw Amerongen G, Bergkamp-Steffens K, Mager W, Planta R (1996) C-terminal domains of general regulatory factors Abf1p and Rap1p in Saccharomyces cerevisiae display functional similarity. Mol Microbiol 19:535–543
Graham IR, Chambers A (1994) Use of a selection technique to identify the diversity of binding sites for the yeast RAP1 transcription factor. Nucleic Acids Res 22:124–130
Graham I, Haw RA, Spink KG, Halden KA, Chambers A (1999) In vivo analysis of functional regions within yeast Rap1p. Mol Cell Biol 19:7481–7490
Grossi S, Bianchi A, Damay P, Shore D (2001) Telomere formation by Rap1p binding site arrays reveals end-specific length regulation requirements and active telomeric recombination. Mol Cell Biol 21:8117–8128
Ha N, Helauer K, Turcotte B (1996) Mutations in target DNA elements of yeast HAP1 modulate its transcriptional activity without affecting DNA binding. Nucleic Acids Res 24:1453–1459
Hardy CF, Balderes D, Shore D (1992) Dissection of a carboxy-terminal region of the yeast regulatory protein RAP1 with effects on both transcriptional activation and silencing. Mol Cell Biol 12:1209–1217
Hermann-Le Denmat S, Werner M, Sentenac A, Thuriaux P (1994) Suppression of yeast RNA polymerase III mutations by FHL1, a gene coding for a forkhead protein involved in rRNA processing. Mol Cel Biol 14:2905–2913
Huie MA, Scott EW, Drazinic CM, López MC, Hornstra IK, Yang TP, Baker HV (1992) Characterization of the DNA-binding activity of GCR1: in vivo evidence for two GCR1-binding sites in the upstream activating sequence of TPI of Saccharomyces cerevisiae. Mol Cell Biol 12:2690–2700
Idrissi F-Z (1999) Structural and functional polymorphism of DNA sequences bound to the S. cerevisiae protein Rap1p (PhD Thesis, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain)
Idrissi F-Z, Piña B (1999) Functional divergence between the half-sites of the DNA binding sequence for Rap1p. Biochem J 341:477–482
Idrissi F-Z, Fernández-Larrea JB, Piña B (1998) Structural and functional heterogeneity of Rap1p complexes with telomeric and UASrpg-like DNA sequences. J Mol Biol 284:925–935
Idrissi F-Z, GarcÃa-Reyero N, Fernández-Larrea J, Piña B (2001) Alternative mechanisms of transcriptional activation by Rap1p. J Biol Chem 276:26090–26098
Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NAD+-dependent histone acetylase. Nature 403:795–800
Jansen R, Gerstein M (2000) Analysis of the yeast transcriptome with structural and functional categories: characterizing highly expressed proteins. Nucleic Acids Res 28:1481–1488
König P, Rhodes D (1997) Recognition of telomeric DNA. Trends Biochem Sci 22:43–47
König P, Giraldo R, Chapman L, Rhodes D (1996) The crystal structure of the DNA-binding domain of yeast RAP1 in complex with telomeric DNA. Cell 85:125–136
Kosoy A., Pagans S, Espinás M, AzorÃn F, Bernués J (2002) GAGA factor down regulates its own promoter. J Biol Chem 277:42280–42282
Krauskopf A, Blackburn EH (1996) Control of telomere growth by interactions of RAP1 with the most distal telomeric repeats. Nature 383:354–357
Kurtz S, Shore D (1991) RAP1 protein activates and silences transcription of mating-type genes in yeast. Genes Dev 5:616–628
Kyrion G, Liu K, Liu C, Lustig AJ (1993) RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. Genes Dev 7:1146–1159
Lascaris RF, Mager WH, Planta RJ (1999) DNA-binding requirements of the yeast protein Rap1p as selected in silico from ribosomal protein gene promoter sequences. Bioinformatics 15:2657–2677
Lee T, et al (2002) Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298:799–804
Lefstin JA, Yamamoto KR (1998) Allosteric effects of DNA on transcriptional regulators. Nature 392:885–888
Lieb JD, Liu X, Botstein D, Brown PO (2001) Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association. Nat Genet 26:327–334
López MC, Smerage JB, Baker HV (1998) Multiple domains of repressor activator protein 1 contribute to facilitated binding of glycolysis regulatory protein 1. Proc Natl Acad Sci USA 95:14112–14117
Loven MA, Likhite VS, Choi I, Nardulli AM (2001) Estrogen response elements alter coactivator recruitment through allosteric modulation of estrogen receptor beta conformation. J Biol Chem 276:45282–45288
Lukens AK, King DA, Marmorstein R (2000) Structure of HAP1-PC7 bound to DNA: implications for DNA recognition and allosteric effects of DNA-binding on transcriptional activation. Nucleic Acids Res28, 3853–3863
Luo K, Vega-Palas M, Grunstein M (2002) Rap1-Sir4 binding independent of other Sir, yKu, or histone interactions initiates the assembly of telomeric heterochromatin in yeast. Genes Dev 16:1528–1539
Martin SG, Laroche T, Suka N, Grunstein M, Gasser SM (1999) Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell 97:621–633
Mencia M, Moqtaderi Z, Geisberg J, Kuras L, Struhl K (2002) Activator-specific recruitment of TFIID and regulation of ribosomal protein genes in yeast. Mol Cell 9:823–833
Mishra K, Shore D (1999) Yeast Ku protein plays a direct role in telomeric silencing and counteracts inhibition by Rif proteins. Curr Biol 9:1123–1126
Mizuta K, Tsujii R, Warner JR, Nishiyama M (1998) The C-terminal silencing domain of Rap1p is essential for the repression of ribosomal protein genes in response to a defect in the secretory pathway. Nucleic Acids Res 26:1063–1069
Moehle CM, Hinnebusch AG (1991) Association of RAP1 binding sites with stringent control of ribosomal protein gene transcription in Saccharomyces cerevisiae. Mol Cell Biol 11:2723–2735
Moretti P, Shore D (2001) Multiple interactions in Sir protein recruitment by Rap1p at silencers and telomeres in yeast. Mol Cell Biol 21:8082–8094
Moretti P, Freeman K, Coodly L, Shore D (1994) Evidence that a complex of SIR proteins interact with the silencer and telomere-binding protein Rap1p. Genes Dev 8:2257–2269
Morse RH (2000) RAP, RAP, open up! New wrinkles for RAP1 in yeast. Trends Genet 15:51–54
O'Reilly M, Teichmann SA, Rhodes D (1999) Telomerases. Curr Opin Struct Biol 9:56–65
Palladino F, Laroche T, Gilson E, Axelrod A, Pillus L, Gasser SM (1993a) SIR3 and SIR4 proteins are required for the positioning and integrity of yeast telomeres. Cell 75:543–555
Palladino F, Laroche T, Gilson E, Pillus L, Gasser SM (1993b) The positioning of yeast telomeres depends on SIR3, SIR4, and the integrity of the nuclear membrane. Cold Spring Harbor Symp Quant Biol 58:733–746
Reid JL, Iyer VR, Brown PO, Struhl K (2000) Coordinate regulation of yeast ribosomal protein genes is associated with targeted recruitment of Esa1 histone acetylase. Mol Cell 6:1297–307
Rossetti L, Cacchione S, De Menna A, Chapman L, Rhodes D, Savino M (2001) Specific interactions of the telomeric protein Rap1p with nucleosomal binding sites. J Mol Biol 305:903–913
Ryan MP, Stafford GA, Yu L, Morse RH (2000) Artificially recruited TATA-binding protein fails to remodel chromatin and does not activate three promoters that require chromatin remodeling. Mol Cell Biol 20:5847–5857
Schwabe JW, Chapman L, Rhodes D (1995) The oestrogen receptor recognizes an imperfectly palindromic response element through an alternative side-chain conformation. Structure 3:201–213
Shore D (1994) RAP1: a protean regulator in yeast. Trends Genet 10:408–412
Stavenhagen JB, Zakian VA (1994) Internal tracts of telomeric DNA act as silencers in Saccharomyces cerevisiae. Genes Dev 8:1411–1422
Taylor HO, O'Reilly M, Leslie AG, Rhodes D (2000) How the multifunctional yeast Rap1p discriminates between DNA target sites: a crystallographic analysis. J Mol Biol 303:693–707
Vignais ML, Woudt LP, Wassenaar GM, Mager WH, Sentenac A, Planta RJ (1987) Specific binding of TUF factor to upstream activation sites of yeast ribosomal protein genes. EMBO J 6:1451–1457
Vignais ML, Huet J, Buhler JM, Sentenac A (1990) Contacts between the factor TUF and RPG sequences. J Biol Chem 265:14669–14674
Wahlin J, Cohn M (2000) Saccharomyces cerevisiae RAP1 binds to telomeric sequences with spatial flexibility. Nucleic Acids Res 28:2292–2301
Warner JR (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24:437–440
Wood JR, Greene GL, Nardulli AM (1998) Estrogen response elements function as allosteric modulators of estrogen receptor concentration. Mol Cell Biol 18:1927–1934
Wotton D, Shore D (1997) A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes Dev 11:748–760
Yu L, Sabet N, Chambers A, Morse RH (2001) The N-terminal and C-terminal domains of RAP1 are dispensable for chromatin opening and GCN4-mediated HIS4 activation in budding yeast. J Biol Chem 276:33257–33264
Acknowledgements
Experimental work included in this review has been supported by grants (BMC2001-0246, and GEN2001-4707-C8-08) from the Ministerio de Ciencia y TecnologÃa (Spain). This study was carried out within the framework of the "Centre de Referència en Biotecnologia" of the Generalitat de Catalunya
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Piña, B., Fernández-Larrea, J., GarcÃa-Reyero, N. et al. The different (sur)faces of Rap1p. Mol Gen Genomics 268, 791–798 (2003). https://doi.org/10.1007/s00438-002-0801-3
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DOI: https://doi.org/10.1007/s00438-002-0801-3