Abstract
Recent biochemical and proteomic approach has identified a CtBP super complex consisting of a host of chromatin modifying enzymes. Analysis of this complex has led to the appreciation that enzymes that mediate deacetylation and histone H3 lysine 9 methylation are present in the same biochemical complex, which facilitates coordinated histone modifications important for establishing repressive chromatin. Importandy, studies of this complex also resulted in the finding of the first histone demethylase LSDI, which represses transcription by demethylating histone K4, where methylation is linked to active transcription. It is anticipated that additional important new insights will be gained from further investigation of this unusual transcriptional repression machine.
CtBP is a transcriptional corepressor and is one of the three main transcriptional cofactors that are directly targeted by the viral oncoprotein E1A during oncogenic transformation.1 To explore mechanisms by which CtBP mediates transcriptional repression, a biochemical approach was taken to isolate proteins that are associated with CtBP. This effort has led to the identification of a CtBP super-complex, consisting of, among others, six potential enzymatic activities.2 While the exact composition of this super-complex may differ in different cell types, characterization of these enzymatic functions in HeLa cells has already provided significant insight into mechanism of action of CtBP and eukaryotic gene regulation. Below we provide a brief discussion of the enzymatic components of the CtBP complex and our current understanding of their individual as well as coordinated enzymatic actions in transcriptional repression. While other aspects of CtBP are covered in other chapters, this chapter is largely confined to the CtBP super complex.
Keywords
- Repressive Chromatin
- Transcriptional Corepressor
- Polycomb Protein
- Chromatin Modify Enzyme
- Histone Deacetylase Complex
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Chinnadurai G. CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Mol Cell 2002; 9:213–224.
Shi YJ, Sawada J-I, Sui GC et al. Coordinated histone modifications mediated by a CtBP corepressor complex. Nature 2003; 422:735–738.
Schaeper U, Boyd JM, Verma S et al. Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation [published erratum appears in Proc Natl Acad Sci USA 1998 Nov 24; 95(24): 14584]. Proc Natl Acad Sci USA 1995; 92(23):10467–10471.
Balasubramanian P, Zhao L-J, Chinnadurai G. Nicotinamide adenine dinucleotide stimulates oligomeriation, interaction with adenovirus E1A and intrinsic dehydrogenase activity of CtBP. FEBS Letters 2003; 537:157–160.
Kumar V, Carlson JE, Ohgi KA et al. Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase. Mol Cell 2002; 10:857–869.
Nardini M, Spano S, Cericola C et al. CtBP/BARS: A dual-function protein involved in transcripttion corepression and Golgi membrane fission. EMBO J 2003; 22(12):3122–3130.
Grooteclaes M, Deveraux Q, Hildebrand J et al. C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs. Proc Natl Acad Sci USA 2003; 100(8):4568–4573.
Sutrias-Grau M, Arnosti DN. CtBP contributes quantitatively to Knirps repression activity in an NAD binding-dependent manner. Mol Cell Biol 2004; 24(13):5953–5966.
Sewalt RG, Gunster MJ, van der Vlag J et al. C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins. Mol Cell Biol 1999; 19(1):777–787.
Kagey MH, Melhuish TA, Wotton D. The polycomb protein Pc2 is a SUMO E3. Cell 2003;113:127–137..
Satijin DP, Olson DJ, vander Vlag J et al. Interference with the expression of a novel human polycomb protein, hPc2, results in cellular transformation and apoptosis. Mol Cell Biol 1997; 17:6076–6086.
Lachner M, O’Carroll D, Rea S et al. Methylatin of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 2001; 410:116–120.
Bannister AJ, Zegerman P, Patridge JF et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 2001; 410:120–124.
Nakayama J-I, Rice JC, Strahl BD et al. Role of histone H3 lysine 9 methylatin in epigenetic control of heterochromatin assembly. Science 2001; 292:110–113.
Kuzmichev A, Nishioka K, Erdjument-Bromage H et al. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev 2002; 16(22):2893–2905.
Min J, Zhang Y, Xu RM. Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. Genes Dev 2003; 17(15):1823–1828.
Fischle W, Wang Y, Jacobs SA et al. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev 2003; 17(15):1870–1881.
Tachibana M, Sugimoto K, Fukushima T et al. SET domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem 2001; 276:25309–25317.
Sundqvist A, Sollerbrant K, Svensson C. The carboxy-terminal region of adenovirus E1A activates transcription through targeting of a C-terminal binding protein-histone deacetylase complex. FEBS Lett 1998; 429(2):183–188.
Koipally J, Georgopoulos K. Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity [In Process Citation]. J Biol Chem 2000; 275(26):19594–19602.
Subramanian T, Chinnadurai G. Association of class I histone deacetylases with transcriptional corepressor CtBP. FEBS Lett 2003; 540(1–3):255–258.
Tachibana M, Ueda J, Fukuda M et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev 2005; 19(7):815–826.
Zhang Y, Reinberg D. Transcription regulation by histone methylation: Interplay between different covalent modifications of the core histone tails. Genes Dev 2001; 15(18):2343–2360.
Humphrey GW, Wang Y, Russanova VR et al. Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/Kiaa0071 and Mta-L1. J Biol Chem 2001; 276:6817–6824.
You A, Tong JK, Grozinger CM et al. CoREST is an integral component of the CoREST-human histone deacetylase complex. Proc Natl Acad Sci USA 2001; 98:1454–1458.
Hakimi MA, Bochar DA, Chenoweth J et al. A coreBRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc Natl Acad Sci USA 2002; 99(11):7420–7425.
Bannister AJ, Schneider R, Kouzarides T. Histone modificaiton: Dynamic or static? Cell 2002; 109:801–806.
Shi Y, Lan F, Matson C et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004; 119(7):941–953.
Litt MD, Simpson M, Gaszner M et al. Correlation between histone lysine methylation and devel opmental changes at the chicken beta-globin locus. Science 2001; 293(5539):2453–2455.
Noma K, Allis CD, Grewal SI. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 2001; 293(5532):1150–1155.
Santos-Rosa H, Schneider R, Bannister AJ et al. Active genes are tri-methylated at K4 of histone H3. Nature 2002; 419:407–411.
Liang G, Lin JC, Wei V et al. Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. Proc Natl Acad Sci USA 2004; 101(19):7357–7362.
Schneider R, Bannister AJ, Myers FA et al. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol 2004; 6(1):73–77.
Lahn BT, Page DC. Retroposition of autosomal mRNA yielded testis-specific gene family on human Y chromosome. Nat Genet 1999; 21:429–433.
Caron C, Pivot-Pajot C, van Grunsven LA et al. Cdyl: A new transcriptional corepressor. EMBO Rep 2003; 4(9):877–882.
Lahn BT, Tang ZL, Zhou JX et al. Previously uncharacterized histone acetyltransferases implicated in mammalian spermatogenesis. Proc Natl Acad Sci USA 2002; 99:8707–8712.
Ballas N, Battaglioli E, Atouf F et al. Regulation of neuronal traits by a novel transcriptional complex. Neuron 2001; 31(3):353–365.
Jarriault S, Greenwald I. Suppressors of the egg-laying defective phenotype of sel-12 presenilin mutants implicate the CoREST corepressor complex in LIN-12/Notch signaling in C. elegans. Genes and Dev 2002; 16:2713–2728.
Eimer S, Lakowski B, Donhauser R et al. Loss of spr-5 bypasses the requirement for the C.elegans presenilin sel-12 by derepressing hop-1. EMBO Jo 2003; 21:5787–5796.
Shi YJ, Matson C, Matson C et al. Regulation of LSD1 histone demethylation activity by its associated factors. Mol Cell Vol 19:857–64.
Lee MG, Wynder C, Cooch N et al. An essential role for CoRESt in nucleosomal histone 3 lysine 4 demethylation. Nature vol 437:432–5.
Grooteclaes ML, Frisch SM. Evidence for a function of CtBP in epithelial gene regulation and anoikis [In Process Citation]. Oncogene 2000; 19(33):3823–3828.
Lunyak W, Burgess R, Prefontaine GG et al. Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science 2002; 298:1747–1752.
Riefler GM, Firestein BL. Binding of neuronal nitric-oxide synthase (nNOS) to carboxyl-terminal-binding protein (CtBP) changes the localization of CtBP from the nucleus to the cytosol: A novel function for targeting by the PDZ domain of nNOS. J Biol Chem 2001; 276(51):48262–48268.
Lin X, Sun B, Liang M et al. Opposed Regulation of Corepressor CtBP by SUMOylation and PDZ Binding. Mol Cell 2003; 11:1389–1396.
Zhang Q, Yoshimatsu Y, Hildebrand J et al. Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP. Cell 2003; 115(2):177–186.
Barnes CJ, Vadlamudi RK, Mishra SK et al. Functional inactivation of a transcriptional corepressor by a signaling kinase. Nat Struct Biol 2003; 10(8):622–628.
Zhang QH, Piston DW, Goodman RH. Regulation of corepressor function by nuclear NADH. Science 2002; 295:1895–1897.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2007 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Shi, YJ., Shi, Y. (2007). CtBP Corepressor Complex. In: GtBP Family Proteins. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-39973-7_8
Download citation
DOI: https://doi.org/10.1007/978-0-387-39973-7_8
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-39971-3
Online ISBN: 978-0-387-39973-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)
