Abstract
A harmonious balance between transcriptional activation and repression in eukaryotes is necessary for a variety of biological phenomena, such as pattern formation, tissue differentiation, and normal development. In this chapter, we will use well-understood cases to provide an overview of the molecular mechanisms by which transcription factors mediate repression.
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References
Adams, M. D., Celniker, S. E., Holt, R. A., Evans, C. A., Gocayne, J. D., Amanatides, P. G., Scherer, S. E., Li, P. W., Hoskins, R. A., Galle, R. F., et al. (2000). The genome sequence of Drosophila melanogaster. Science 287, 2185–2195.
Ammanamanchi, S., Freeman, J. W., and Brattain, M. G. (2003). Acetylated sp3 is a transcriptional activator. J Biol Chem 278, 35775–35780.
Andrau, J. C., Van Oevelen, C. J., Van Teeffelen, H. A., Weil, P. A., Holstege, F. C., and Timmers, H. T. (2002). Mot1p is essential for TBP recruitment to selected promoters during in vivo gene activation. Embo J 21, 5173–5183.
Arnosti, D. N., Barolo, S., Levine, M., and Small, S. (1996a). The eve stripe 2 enhancer employs multiple modes of transcriptional synergy. Development 122, 205–214.
Arnosti, D. N., Gray, S., Barolo, S., Zhou, J., and Levine, M. (1996b). The gap protein knirps mediates both quenching and direct repression in the Drosophila embryo. Embo j 15, 3659–3666.
Auble, D. T., Hansen, K. E., Mueller, C. G., Lane, W. S., Thorner, J., and Hahn, S. (1994). Mot1, a global repressor of RNA polymerase II transcription, inhibits TBP binding to DNA by an ATP-dependent mechanism. Genes Dev 8, 1920–1934.
Austin, R. J., and Biggin, M. D. (1995). A domain of the even-skipped protein represses transcription by preventing TFIID binding to a promoter: repression by cooperative blocking. Mol Cell Biol 15, 4683–4693.
Baek, S. H., and Rosenfeld, M. G. (2004). Nuclear receptor coregulators: their modification codes and regulatory mechanism by translocation. Biochem Biophys Res Commun 319, 707–714.
Balasubramanian, P., Zhao, L. J., and Chinnadurai, G. (2003). Nicotinamide adenine dinucleotide stimulates oligomerization, interaction with adenovirus E1A and an intrinsic dehydrogenase activity of CtBP. FEBS Lett 537, 157–160.
Baniahmad, A., Ha, I., Reinberg, D., Tsai, S., Tsai, M. J., and O’Malley, B. W. (1993). Interaction of human thyroid hormone receptor beta with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc Natl Acad Sci USA 90, 8832–8836.
Barolo, S., and Levine, M. (1997). hairy mediates dominant repression in the Drosophila embryo. Embo j 16, 2883–2891.
Barolo, S., and Posakony, J. W. (2002). Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev 16, 1167–1181.
Barolo, S., Stone, T., Bang, A. G., and Posakony, J. W. (2002). Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless. Genes Dev 16, 1964–1976.
Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L., and Weintraub, H. (1990). The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61, 49–59.
Berman, B. P., Nibu, Y., Pfeiffer, B. D., Tomancak, P., Celniker, S. E., Levine, M., Rubin, G. M., and Eisen, M. B. (2002). Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome. Proc Natl Acad Sci USA 99, 757–762.
Breiling, A., Turner, B. M., Bianchi, M. E., and Orlando, V. (2001). General transcription factors bind promoters repressed by Polycomb group proteins. Nature 412, 651–655.
Burke, L. J., and Baniahmad, A. (2000). Co-repressors 2000. Faseb J 14, 1876–1888.
Burley, S. K., and Roeder, R. G. (1998). TATA box mimicry by TFIID: autoinhibition of pol II transcription. Cell 94, 551–553.
Cai, H. N., Arnosti, D. N., and Levine, M. (1996). Long-range repression in the Drosophila embryo. Proc Natl Acad Sci USA 93, 9309–9314.
Campbell, G., and Tomlinson, A. (1999). Transducing the Dpp morphogen gradient in the wing of Drosophila: regulation of Dpp targets by brinker. Cell 96, 553–562.
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., and Zhang, Y. (2002). Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039–1043.
Cao, R., and Zhang, Y. (2004). The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr Opin Genet Dev 14, 155–164.
Cavallo, R. A., Cox, R. T., Moline, M. M., Roose, J., Polevoy, G. A., Clevers, H., Peifer, M., and Bejsovec, A. (1998). Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395, 604–608.
Celniker, S. E., and Rubin, G. M. (2003). The Drosophila melanogaster genome. Annu Rev Genomics Hum Genet 4, 89–117.
Chang, Y. L., Peng, Y. H., Pan, I. C., Sun, D. S., King, B., and Huang, D. H. (2001). Essential role of Drosophila Hdac1 in homeotic gene silencing. Proc Natl Acad Sci USA 98, 9730–9735.
Chen, G., Fernandez, J., Mische, S., and Courey, A. J. (1999). A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development. Genes Dev 13, 2218–2230.
Chicca, J. J., 2nd, Auble, D. T., and Pugh, B. F. (1998). Cloning and biochemical characterization of TAF-172, a human homolog of yeast Motl. Mol Cell Biol 18, 1701–1710.
Chinnadurai, G. (2002). CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Mol Cell 9, 213–224.
Clyde, D. E., Corado, M. S., Wu, X., Pare, A., Papatsenko, D., and Small, S. (2003). A self-organizing system of repressor gradients established segmental complexity in Drosophila. Nature 426, 849–853.
Courey, A. J., and Jia, S. (2001). Transcriptional repression: the long and the short of it. Genes Dev 15, 2786–2796.
Cowden, J., and Levine, M. (2003). Ventral dominance governs sequential patterns of gene expression across the dorsal-ventral axis of the neuroectoderm in the Drosophila embryo. Dev Biol 262, 335–349.
Cress, W. D., and Seto, E. (2000). Histone deacetylases, transcriptional control, and cancer. J Cell Physiol 184, 1–16.
Creton, S., Svejstrup, J. Q., and Collart, M. A. (2002). The NC2 alpha and beta subunits play different roles in vivo. Genes Dev 16, 3265–3276.
Czermin, B., Melfi, R., McCabe, D., Seitz, V., Imhof, A., and Pirrotta, V. (2002). Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111, 185–196.
Danzer, J. R., and Wallrath, L. L. (2004). Mechanisms of HP1-mediated gene silencing in Drosophila. Development 131, 3571–3580.
Dasgupta, A., Darst, R. P., Martin, K. J., Afshari, C. A., and Auble, D. T. (2002). Motl activates and represses transcription by direct, ATPase-dependent mechanisms. Proc Natl Acad Sci USA 99, 2666–2671.
Dehal, P., Satou, Y., Campbell, R. K., Chapman, J., Degnan, B., De Tomaso, A., Davidson, B., Di Gregorio, A., Gelpke, M., Goodstein, D. M., et al. (2002). The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298, 2157–2167.
Dellino, G. I., Schwartz, Y. B., Farkas, G., McCabe, D., Elgin, S. C., and Pirrotta, V. (2004). Polycomb silencing blocks transcription initiation. Mol Cell 13, 887–893.
Dikstein, R., Ruppert, S., and Tjian, R. (1996). TAFI1250 is a bipartite protein kinase that phosphorylates the base transcription factor RAP74. Cell 84, 781–790.
Dubnicoff, T., Valentine, S. A., Chen, G., Shi, T., Lengyel, J. A., Paroush, Z., and Courey, A. J. (1997). Conversion of dorsal from an activator to a repressor by the global corepressor Groucho. Genes Dev 11, 2952–2957.
Ferreira, R., Naguibneva, I., Pritchard, L. L., Ait-Si-Ali, S., and Harel-Bellan, A. (2001). The Rb/chromatin connection and epigenetic control: opinion. Oncogene 20, 3128–3133.
Fitzgerald, D. P., and Bender, W. (2001). Polycomb group repression reduces DNA accessibility. Mol Cell Biol 21, 6585–6597.
Fondell, J. D., Brunel, F., Hisatake, K., and Roeder, R. G. (1996). Unliganded thyroid hormone receptor alpha can target TATA-binding protein for transcriptional repression. Mol Cell Biol 16, 281–287.
Fondell, J. D., Roy, A. L., and Roeder, R. G. (1993). Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. Genes Dev 7, 1400–1410.
Fujioka, M., Emi-Sarker, Y., Yusibova, G. L., Goto, T., and Jaynes, J. B. (1999). Analysis of an even-skipped rescue transgene reveals both composite and discrete neuronal and early blastoderm enhancers, and multi-stripe positioning by gap gene repressor gradients. Development 126, 2527–2538.
Gaston, K., and Jayaraman, P. S. (2003). Transcriptional repression in eukaryotes: repressors and repression mechanisms. Cell Mol Life Sci 60, 721–741.
Geisberg, J. V., Moqtaderi, Z., Kuras, L., and Struhl, K. (2002). Motl associates with transcriptionally active promoters and inhibits association of NC2 in Saccharomyces cerevisiae. Mol Cell Biol 22, 8122–8134.
Gill, G. (2004). SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev 18, 2046–2059.
Glass, C. K., and Rosenfeld, M. G. (2000). The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14, 121–141.
Goppelt, A., Stelzer, G., Lottspeich, F., and Meisterernst, M. (1996). A mechanism for repression of class II gene transcription through specific binding of NC2 to TBP-promoter complexes via heterodimeric histone fold domains. Embo j 15, 3105–3116.
Gould, A. (1997). Functions of mammalian Polycomb group and trithorax group related genes. Curr Opin Genet Dev 7, 488–494.
Grandori, C., Cowley, S. M., James, L. P., and Eisenman, R. N. (2000). The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 16, 653–699.
Gray, S., and Levine, M. (1996a). Short-range transcriptional repressors mediate both quenching and direct repression within complex loci in Drosophila. Genes Dev 10, 700–710.
Gray, S., and Levine, M. (1996b). Transcriptional repression in development. Curr Opin Cell Biol 8, 358–364.
Gray, S., Szymanski, P., and Levine, M. (1994). Short-range repression permits multiple enhancers to function autonomously within a complex promoter. Genes Dev 8, 1829–1838.
Grooteclaes, M., Deveraux, Q., Hildebrand, J., Zhang, Q., Goodman, R. H., and Frisch, S. M. (2003). C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs. Proc Natl Acad Sci USA 100, 4568–4573.
Gunster, M., raaphorst, F., Hamer, K., den Blaauwen, J., Fieret, E., Meijer, C., and Otte, A. (2001). Differential expression of human Polycomb group proteins in various tissues and cell types. J Cell Biochem 81(S36), 129–143.
Hanna-Rose, W., and Hansen, U. (1996). Active repression mechanisms of eukaryotic transcription repressors. Trends Genet 12, 229–234.
Hanna-Rose, W., Licht, J. D., and Hansen, U. (1997). Two evolutionarily conserved repression domains in the Drosophila Kruppel protein differ in activator specificity. Mol Cell Biol 17, 4820–4829.
Hasson, P., Egoz, N., Winkler, C., Volohonsky, G., Jia, S., Dinur, T., Volk, T., Courey, A. J., and Paroush, Z. (2005). EGFR signaling attenuates Groucho-dependent repression to antagonize Notch transcriptional output. Nat Genet 37, 101–105.
Hasson, P., Muller, B., Basler, K., and Paroush, Z. (2001). Brinker requires two corepressors for maximal and versatile repression in Dpp signalling. Embo J 20, 5725–5736.
Hayashi, Y., Wang, W., Ninomiya, T., Nagano, H., Ohta, K., and Itoh, H. (1999). Liver enriched transcription factors and differentiation of hepatocellular carcinoma. Mol Pathol 52, 19–24.
Heinzel, T., Lavinsky, R. M., Mullen, T. M., Soderstrom, M., Laherty, C. D., Torchia, J., Yang, W. M., Brard, G., Ngo, S. D., Davie, J. R., et al. (1997). A complex containing N-CoR, Sin3 and histone deacetylase mediates transcriptional repression. Nature 387, 43–48.
Hewitt, G. F., Strunk, B. S., Margulies, C., Priputin, T., Wang, X. D., Amey, R., Pabst, B. A., Kosman, D., Reinitz, J., and Arnosti, D. N. (1999). Transcriptional repression by the Drosophila giant protein: cis element positioning provides an alternative means of interpreting an effector gradient. Development 126, 1201–1210.
Hoch, M., Gerwin, N., Taubert, H., and Jackle, H. (1992). Competition for overlapping sites in the regulatory region of the Drosophila gene Kruppel. Science 256, 94–97.
Horlein, A. J., Naar, A. M., Heinzel, T., Torchia, J., Gloss, B., Kurokawa, R., Ryan, A., Kamei, Y., Soderstrom, M., Glass, C. K., and et al. (1995). Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 377, 397–404.
Hunter, T., and Karin, M. (1992). The regulation of transcription by phosphorylation. Cell 70, 375–387.
Igarashi, K., Kataoka, K., Itoh, K., Hayashi, N., Nishizawa, M., and Yamamoto, M. (1994). Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature 367, 568–572.
Imai, K. S., Hino, K., Yagi, K., Satoh, N., and Satou, Y. (2004). Gene expression profiles of transcription factors and signaling molecules in the ascidian embryo: towards a comprehensive understanding of gene networks. Development 131, 4047–4058.
Ip, Y. T., and Hemavathy, K. (1997). Drosophila development. Delimiting patterns by repression. Curr Biol 7, R216–218.
Ip, Y. T., Park, R. E., Kosman, D., Bier, E., and Levine, M. (1992). The dorsal gradient morphogen regulates stripes of rhomboid expression in the presumptive neuroectoderm of the Drosophila embryo. Genes Dev 6, 1728–1739.
Iratni, R., Yan, Y. T., Chen, C., Ding, J., Zhang, Y., Price, S. M., Reinberg, D., and Shen, M. M. (2002). Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1. Science 298, 1996–1999.
Jackle, H., Hoch, M., Pankratz, M. J., Gerwin, N., Sauer, F., and Bronner, G. (1992). Transcriptional control by Drosophila gap genes. J Cell Sci Suppl 16, 39–51.
Jacobson, R. H., Ladurner, A. G., King, D. S., and Tjian, R. (2000). Structure and function of a human TAFII250 double bromodomain module. Science 288, 1422–1425.
Jazwinska, A., Kirov, N., Wieschaus, E., Roth, S., and Rushlow, C. (1999). The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation. Cell 96, 563–573.
Jen, Y., Weintraub, H., and Benezra, R. (1992). Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins. Genes Dev 6, 1466–1479.
Jenuwein, T. (2001). Re-SET-ting heterochromatin by histone methyltransferases. Trends Cell Biol 11, 266–273.
Jiang, G., and Sladek, F. M. (1997). The DNA binding domain of hepatocyte nuclear factor 4 mediates cooperative, specific binding to DNA and heterodimerization with the retinoid X receptor alpha. J Biol Chem 272, 1218–1225.
Jimenez, G., Guichet, A., Ephrussi, A., and Casanova, J. (2000). Relief of gene repression by torso RTK signaling: role of capicua in Drosophila terminal and dorsoventral patterning. Genes Dev 14, 224–231.
Johnson, A. D. (1995). The price of repression. Cell 81, 655–658.
Kamada, K., Shu, F., Chen, H., Malik, S., Stelzer, G., Roeder, R. G., Meisterernst, M., and Burley, S. K. (2001). Crystal structure of negative cofactor 2 recognizing the TBP-DNA transcription complex. Cell 106, 71–81.
Keller, S. A., Mao, Y., Struffi, P., Margulies, C., Yurk, C. E., Anderson, A. R., Amey, R. L., Moore, S., Ebels, J. M., Foley, K., et al. (2000). dCtBP-dependent and-independent repression activities of the Drosophila Knirps protein. Mol Cell Biol 20, 7247–7258.
Kimura, A., Nishiyori, A., Murakami, T., Tsukamoto, T., Hata, S., Osumi, T., Okamura, R., Mori, M., and Takiguchi, M. (1993). Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4). J Biol Chem 268, 11125–11133.
Kirkpatrick, H., Johnson, K., and Laughon, A. (2001). Repression of dpp targets by binding of brinker to mad sites. J Biol Chem 276, 18216–18222.
Klejman, M. P., Pereira, L. A., van Zeeburg, H. J., Gilfillan, S., Meisterernst, M., and Timmers, H. T. (2004). NC2alpha interacts with BTAF1 and stimulates its ATP-dependent association with TATA-binding protein. Mol Cell Biol 24, 10072–10082.
Kobayashi, M., Goldstein, R. E., Fujioka, M., Paroush, Z., and Jaynes, J. B. (2001). Groucho augments the repression of multiple Even skipped target genes in establishing parasegment boundaries. Development 128, 1805–1815.
Kokubo, T., Yamashita, S., Horikoshi, M., Roeder, R. G., and Nakatani, Y. (1994). Interaction between the N-terminal domain of the 230-kDa subunit and the TATA box-binding subunit of TFIID negatively regulates TATA-box binding. Proc Natl Acad Sci USA 91, 3520–3524.
Kotani, T., Banno, K., Ikura, M., Hinnebusch, A. G., Nakatani, Y., Kawaichi, M., and Kokubo, T. (2000). A role of transcriptional activators as antirepressors for the autoinhibitory activity of TATA box binding of transcription factor IID. Proc Natl Acad Sci USA 97, 7178–7183.
Kumar, V., Carlson, J. E., Ohgi, K. A., Edwards, T. A., Rose, D. W., Escalante, C. R., Rosenfeld, M. G., and Aggarwal, A. K. (2002). Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase. Mol Cell 10, 857–869.
Ladias, J. A., Hadzopoulou-Cladaras, M., Kardassis, D., Cardot, P., Cheng, J., Zannis, V., and Cladaras, C. (1992). Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, ARP-1, EAR-2, and EAR-3. J Biol Chem 267, 15849–15860.
Laherty, C. D., Yang, W. M., Sun, J. M., Davie, J. R., Seto, E., and Eisenman, R. N. (1997). Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell 89, 349–356.
Lai, E. C. (2002). Keeping a good pathway down: transcriptional repression of Notch pathway target genes by CSL proteins. EMBO Rep 3, 840–845.
Lania, L., Majello, B., and De Luca, P. (1997). Transcriptional regulation by the Sp family proteins. Int J Biochem Cell Biol 29, 1313–1323.
Lassar, A. B., Davis, R. L., Wright, W. E., Kadesch, T., Murre, C., Voronova, A., Baltimore, D., and Weintraub, H. (1991). Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell 66, 305–315.
Lee, T. I., and Young, R. A. (1998). Regulation of gene expression by TBP-associated proteins. Genes Dev 12, 1398–1408.
Lemaire, M., Xie, J., Meisterernst, M., and Collart, M. A. (2000). The NC2 repressor is dispensable in yeast mutated for the Sin4p component of the holoenzyme and plays roles similar to Mot1p in vivo. Mol Microbiol 36, 163–173.
Lemon. B., and Tjian. R. (2000). Orchestrated response: a symphony of transcription factors for gene control. Genes Dev 14, 2551–2569.
Levine, M., and Manley, J. L. (1989). Transcriptional repression of eukaryotic promoters. Cell 59, 405–408.
Li, C., and Manley, J. L. (1998). Even-skipped represses transcription by binding TATA binding protein and blocking the TFIID-TATA box interaction. Mol Cell Biol 18, 3771–3781.
Licht, J. D., Hanna-Rose, W., Reddy, J. C., English, M. A., Ro, M., Grossel, M., Shaknovich, R., and Hansen, U. (1994). Mapping and mutagenesis of the amino-terminal transcriptional repression domain of the Drosophila Kruppel protein. Mol Cell Biol 14, 4057–4066.
Lin, X., Sun, B., Liang, M., Liang, Y. Y., Gast, A., Hildebrand, J., Brunicardi, F. C., Melchior, F., and Feng, X. H. (2003). Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding. Mol Cell 11, 1389–1396.
Liu, D., Ishima, R., Tong, K. I., Bagby, S., Kokubo, T., Muhandiram, D. R., Kay, L. E., Nakatani, Y., and Ikura, M. (1998). Solution structure of a TBP-TAF(II)230 complex: protein mimicry of the minor groove surface of the TATA box unwound by TBP. Cell 94, 573–583.
Lund, A. H., and van Lohuizen, M. (2004). Polycomb complexes and silencing mechanisms. Curr Opin Cell Biol 16, 239–246.
Luscher, B. (2001). Function and regulation of the transcription factors of the Myc/Max/Mad network. Gene 277, 1–14.
Majello, B., De Luca, P., and Lania, L. (1997). Sp3 is a bifunctional transcription regulator with modular independent activation and repression domains. J Biol Chem 272, 4021–4026.
Mannervik, M., and Levine, M. (1999). The Rpd3 histone deacetylase is required for segmentation of the Drosophila embryo. Proc Natl Acad Sci USA 96, 6797–6801.
Mannervik, M., Nibu, Y., Zhang, H., and Levine, M. (1999). Transcriptional coregulators in development. Science 284, 606–609.
Mermelstein, F., Yeung, K., Cao, J., Inostroza, J. A., Erdjument-Bromage, H., Eagelson, K., Landsman, D., Levitt, P., Tempst, P., and Reinberg, D. (1996). Requirement of a corepressor for Drl-mediated repression of transcription. Genes Dev 10, 1033–1048.
Mietus-Snyder, M., Sladek, F. M., Ginsburg, G. S., Kuo, C. F., Ladias, J. A., Darnell, J. E., Jr., and Karathanasis, S. K. (1992). Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mol Cell Biol 12, 1708–1718.
Minami, M., Kinoshita, N., Kamoshida, Y., Tanimoto, H., and Tabata, T. (1999). brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes. Nature 398, 242–246.
Misra, S., Crosby, M. A., Mungall, C. J., Matthews, B. B., Campbell, K. S., Hradecky, P., Huang, Y., Kaminker, J. S., Millburn. G. H., Prochnik, S. E., et al. (2002). Annotation of the Drosophila melanogaster euchromatic genome: a systematic review. Genome Biol 3, RESEARCH0083.
Mizzen, C. A., Yang, X. J., Kokubo, T., Brownell, J. E., Bannister, A. J., Owen-Hughes, T., Workman, J., Wang, L., Berger, S. L., Kouzarides, T., et al. (1996). The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell 87, 1261–1270.
Motohashi, H., Shavit, J. A., Igarashi, K., Yamamoto, M., and Engel, J. D. (1997). The world according to Maf. Nucleic Acids Res 25, 2953–2959.
Nibu, Y., and Levine, M. S. (2001). CtBP-dependent activities of the short-range Giant repressor in the Drosophila embryo. Proc Natl Acad Sci USA 98, 6204–6208.
Nibu, Y., Senger, K., and Levine, M. (2003). CtBP-independent repression in the Drosophila embryo. Mol Cell Biol 23, 3990–3999.
Nibu, Y., Zhang, H., Bajor, E., Barolo, S., Small, S., and Levine, M. (1998a). dCtBP mediates transcriptional repression by Knirps, Kruppel and Snail in the Drosophila embryo. Embo J 17, 7009–7020.
Nibu, Y., Zhang, H., and Levine, M. (1998b). Interaction of short-range repressors with Drosophila CtBP in the embryo. Science 280, 101–104.
Nibu, Y., Zhang, H., and Levine, M. (2001). Local action of long-range repressors in the Drosophila embryo. Embo J 20, 2246–2253.
Nishikawa, J., Kokubo, T., Horikoshi, M., Roeder, R. G., and Nakatani, Y. (1997). Drosophila TAF(II)230 and the transcriptional activator VP16 bind competitively to the TATA box-binding domain of the TATA box-binding protein. Proc Natl Acad Sci USA 94, 85–90.
Ochoa-Espinosa, A., Yucel, G., Kaplan, L., Pare, A., Pura, N., Oberstein, A., Papatsenko, D., and Small, S. (2005). The role of binding site cluster strength in Bicoid-dependent patterning in Drosophila. Proc Natl Acad Sci USA.
Orlando, V. (2003). Polycomb, epigenomes, and control of cell identity. Cell 112, 599–606.
Orlando, V., Jane, E. P., Chinwalla, V., Harte, P. J., and Paro, R. (1998). Binding of trithorax and Polycomb proteins to the bithorax complex: dynamic changes during early Drosophila embryogenesis. Embo J 17, 5141–5150.
Orlando, V., and Paro, R. (1995). Chromatin multiprotein complexes involved in the maintenance of transcription patterns. Curr Opin Genet Dev 5, 174–179.
Orlando, V., and Paro, V. (1993). Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin. Cell 75, 1187–1198.
Otte, A. P., and Kwaks, T. H. (2003). Gene repression by Polycomb group protein complexes: a distinct complex for every occasion? Curr Opin Genet Dev 13, 448–454.
Park, J. I., Tsai, S. Y., and Tsai, M. J. (2003). Molecular mechanism of chicken ovalbumin upstream promoter-transcription factor (COUP-TF) actions. Keio J Med 52, 174–181.
Perdomo, J., Verger, A., Turner, J., and Crossley, M. (2005). Role for SUMO modification in facilitating transcriptional repression by BKLF. Mol Cell Biol 25, 1549–1559.
Pereira, F. A., Tsai, M. J., and Tsai, S. Y. (2000). COUP-TF orphan nuclear receptors in development and differentiation. Cell Mol Life Sci 57, 1388–1398.
Pereira, L. A., Klejman, M. P., and Timmers, H. T. (2003). Roles for BTAF1 and Mot1p in dynamics of TATA-binding protein and regulation of RNA polymerase II transcription. Gene 315, 1–13.
Pham, A. D., and Sauer, F. (2000). Ubiquitin-activating/conjugating activity of TAFII250, a mediator of activation of gene expression in Drosophila. Science 289, 2357–2360.
Phippen, T. M., Sweigart, A. L., Moniwa, M., Krumm, A., Davie, J. R., and Parkhurst, S. M. (2000). Drosophila C-terminal binding protein functions as a context-dependent transcriptional co-factor and interferes with both mad and groucho transcriptional repression. J Biol Chem 275, 37628–37637.
Pirrotta, V. (1999). Polycomb silencing and the maintenance of stable chromatin states. In Results and problems in cell differentiation: genomic imprinting., R. Ohlsson, ed. (Berlin, Germany, Springer-Verlag), pp. 205–228.
Pirrotta, V., Poux, S., Melfi, R., and Pilyugin, M. (2003). Assembly of Polycomb complexes and silencing mechanisms. Genetica 117, 191–197.
Prelich, G. (1997). Saccharomyces cerevisiae BUR6 encodes a DRAP1/NC2alpha homolog that has both positive and negative roles in transcription in vivo. Mol Cell Biol 17, 2057–2065.
Pugh, B. F. (2000). Control of gene expression through regulation of the TATA-binding protein. Gene 255, 1–14.
Ramji, D. P., and Foka, P. (2002). CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem J 365, 561–575.
Riechmann, J. L., Heard, J., Martin, G., Reuber, L., Jiang, C., Keddie, J., Adam, L., Pineda, O., Ratcliffe, O. J., Samaha, R. R., et al. (2000). Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes. Science 290, 2105–2110.
Ron, D., and Habener, J. F. (1992). CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev 6, 439–453.
Roose, J., and Clevers, H. (1999). TCF transcription factors: molecular switches in carcinogenesis. Biochim Biophys Acta 1424, M23–37.
Rosenberg, M. I., and Parkhurst, S. M. (2002). Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination. Cell 109, 447–458.
Rushlow, C., Colosimo, P. F., Lin, M. C., Xu, M., and Kirov, N. (2001). Transcriptional regulation of the Drosophila gene zen by competing Smad and Brinker inputs. Genes Dev 15, 340–351.
Ryu, J. R., and Arnosti, D. N. (2003). Functional similarity of Knirps CtBP-dependent and CtBP-independent transcriptional repressor activities. Nucleic Acids Res 31, 4654–4662.
Saller, E., and Bienz, M. (2001). Direct competition between Brinker and Drosophila Mad in Dpp target gene transcription. EMBO Rep 2, 298–305.
Satou, Y., Takatori, N., Yamada, L., Mochizuki, Y., Hamaguchi, M., Ishikawa, H., Chiba, S., Imai, K., Kano, S., Murakami, S. D., et al. (2001). Gene expression profiles in Ciona intestinalis tailbud embryos. Development 128, 2893–2904.
Sauer, F., Fondell, J. D., Ohkuma, Y., Roeder, R. G., and Jackle, H. (1995). Control of transcription by Kruppel through interactions with TFIIB and TFIIE beta. Nature 375, 162–164.
Saurin, A. J., Shao, Z., Erdjument-Bromage, H., Tempst, P., and Kingston, R. E. (2001). A Drosophila Polycomb group complex includes Zeste and dTAFII proteins. Nature 412, 655–660.
Shao, Z., Raible, F., Mollaaghababa, R., Guyon, J. R., Wu, C. T., Bender, W., and Kingston, R. E. (1999). Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 98, 37–46.
Shi, Y., Sawada, J., Sui, G., Affar el, B., Whetstine, J. R., Lan, F., Ogawa, H., Luke, M. P., and Nakatani, Y. (2003). Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature 422, 735–738.
Small, S., Arnosti, D. N., and Levine, M. (1993). Spacing ensures autonomous expression of different stripe enhancers in the even-skipped promoter. Development 119, 762–772.
Small, S., Blair, A., and Levine, M. (1992). Regulation of even-skipped stripe 2 in the Drosophila embryo. Embo J 11, 4047–4057.
Small, S., Blair, A., and Levine, M. (1996). Regulation of two pair-rule stripes by a single enhancer in the Drosophila embryo. Dev Biol 175, 314–324.
Small, S., Kraut, R., Hoey, T., Warrior, R., and Levine, M. (1991). Transcriptional regulation of a pair-rule stripe in Drosophila. Genes Dev 5, 827–839.
Song, H., Hasson, P., Paroush, Z., and Courey, A. J. (2004). Groucho oligomerization is required for repression in vivo. Mol Cell Biol 24, 4341–4350.
Stanojevic, D., Small, S., and Levine, M. (1991). Regulation of a segmentation stripe by overlapping activators and repressors in the Drosophila embryo. Science 254, 1385–1387.
Stathopoulos, A., and Levine, M. (2002). Dorsal gradient networks in the Drosophila embryo. Dev Biol 246, 57–67.
Struffi, P., Corado, M., Kulkarni, M., and Arnosti, D. N. (2004). Quantitative contributions of CtBP-dependent and-independent repression activities of Knirps. Development 131, 2419–2429.
Suske, G. (1999). The Sp-family of transcription factors. Gene 238, 291–300.
Sutrias-Grau, M., and Arnosti, D. N. (2004). CtBP contributes quantitatively to Knirps repression activity in an NAD binding-dependent manner. Mol Cell Biol 24, 5953–5966.
Takaki, T., Fukasawa, K., Suzuki-Takahashi, I., and Hirai, H. (2004). Cdk-mediated phosphorylation of pRB regulates HDAC binding in vitro. Biochem Biophys Res Commun 316, 252–255.
Takizawa, T., Nakashima, K., Namihira, M., Ochiai, W., Uemura, A., Yanagisawa, M., Fujita, N., Nakao, M., and Taga, T. (2001). DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain. Dev Cell 1, 749–758.
Thiel, G., Lietz, M., and Hohl, M. (2004). How mammalian transcriptional repressors work. Eur J Biochem 271, 2855–2862.
Tie, F., Furuyama, T., Prasad-Sinha, J., Jane, E., and Harte, P. (2001). The Drosophila polycom group proteins ESC and E(Z) are present in a complex containing the histone-binding protein p55 and the histone deacetylase RPD3. Development 128, 275–286.
Tomancak, P., Beaton, A., Weiszmann, R., Kwan, E., Shu, S., Lewis, S. E., Richards, S., Ashburner, M., Hartenstein, V., Celniker, S. E., and Rubin, G. M. (2002). Systematic determination of patterns of gene expression during Drosophila embryogenesis. Genome Biol 3, RESEARCH0088.
Turner, J., and Crossley, M. (1998). Cloning and characterization of mCtBP2, a co-repressor that associates with basic Kruppel-like factor and other mammalian transcriptional regulators. Embo J 17, 5129–5140.
Turner, J., and Crossley, M. (2001). The CtBP family: enigmatic and enzymatic transcriptional co-repressors. Bioessays 23, 683–690.
Um, M., Li, C., and Manley, J. L. (1995). The transcriptional repressor even-skipped interacts directly with TATA-binding protein. Mol Cell Biol 15, 5007–5016.
Valentine, S. A., Chen, G., Shandala, T., Fernandez, J., Mische, S., Saint, R., and Courey, A. J. (1998). Dorsal-mediated repression requires the formation of a multiprotein repression complex at the ventral silencer. Mol Cell Biol 18, 6584–6594.
van der Vlag, J., and Otte, A. (1999). Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat Genet 23, 474–478.
Viollet, B., Kahn, A., and Raymondjean, M. (1997). Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4. Mol Cell Biol 17, 4208–4219.
Wade, P. (2001). Methyl CpG-binding proteins and transcriptional repression. BioEssays 23, 1131–1137.
Waltzer, L., and Bienz, M. (1998). Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling. Nature 395, 521–525.
Wang, L., Brown, J. L., Cao, R., Zhang, Y., Kassis, J. A., and Jones, R. S. (2004). Hierarchical recruitment of polycomb group silencing complexes. Mol Cell 14, 637–646.
Willy, P. J., Kobayashi, R., and Kadonaga, J. T. (2000). A basal transcription factor that activates or represses transcription. Science 290, 982–985.
Winter, S. E., and Campbell, G. (2004). Repression of Dpp targets in the Drosophila wing by Brinker. Development 131, 6071–6081.
Yang, X.-J., and Seto, E. (2003). Collaborative spirit of histone deacetylases in regulating chromatin structure and gene expression. Curr Opin Genet Dev 13, 143–153.
Yu, B., Datta, P. K., and Bagchi, S. (2003). Stability of the Sp3-DNA complex is promoter-specific: Sp3 efficiently competes with Sp1 for binding to promoters containing multiple Sp-sites. Nucleic Acids Res 31, 5368–5376.
Zhang, Q., Piston, D. W., and Goodman, R. H. (2002a). Regulation of corepressor function by nuclear NADH. Science 295, 1895–1897.
Zhang, Q., Yao, H., Vo, N., and Goodman, R. H. (2000). Acetylation of adenovirus E1A regulates binding of the transcriptional corepressor CtBP. Proc Natl Acad Sci USA 97, 14323–14328.
Zhang, S., Xu, L., Lee, J., and Xu, T. (2002b). Drosophila atrophin homolog functions as a transcriptional corepressor in multiple developmental processes. Cell 108, 45–56.
Zink, D., and Paro, R. (1995). Drosophila Polycomb-group regulated chromatin inhibits the accessibility of a trans-activator to its target DNA. Embo J 14, 5660–5671.
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Perrone, L., Aihara, H., Nibu, Y. (2006). Transcriptional Repressors and Repression Mechanisms. In: Ma, J. (eds) Gene Expression and Regulation. Springer, New York, NY. https://doi.org/10.1007/978-0-387-40049-5_9
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