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Duhamel, Marianne (2007) Régulation épigénétique de l'expression du facteur de transcription hématopoïétique Aiolos et implication dans la leucémie lymphoïde chronique. Doctorat Immunologie / Hématologie, INSERM U543, Immunologie Cellulaire et Tissulaire, AgroParistech 2007AGPT0031 p.382.
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Résumé
Le facteur de transcription Aiolos, membre de la famille des protéines à doigts de zinc de type Ikaros, joue un rôle important dans la différenciation des lymphocytes B.
Notre premier objectif a été de définir les mécanismes impliqués dans la régulation de la transcription du gène aiolos humain. Nous avons analysé la méthylation de l’îlot CpG d’Aiolos et les modifications de ses histones dans différentes lignées et cellules primaires. Nous avons observé une méthylation dense de l’ilot CpG, associée à des niveaux faibles de marques d’euchromatine (H3K4 di-/tri-méthylées, H3K9 acétylées) dans les lignées Aiolos négatives U937 et 1106mel, tandis que les cellules exprimant Aiolos présentaient les caractéristiques opposées. L’inhibition des Dnmt dans les U937 et 1106mel avec la 5-Aza-dC a entrainé une déméthylation de l’îlot CpG, associée à une augmentation des marques d’euchromatine et à une induction d’Aiolos. La répression d’Aiolos dans les monocytes et mélanocytes primaires a quant à elle été associée à une augmentation des H3K9me3 et H3K27me3, indépendamment de la méthylation de l’ADN.
Notre deuxième objectif était d’étudier l’implication d’Aiolos dans les syndromes lymphoprolifératifs des cellules B matures chez l’homme (leucémie lymphoïde chronique et autres lymphomes B). Nous avons démontré que les cellules B, saines et tumorales, exprimaient majoritairement le variant hAio1 (80%) et nous avons observé pour la première fois une augmentation globale des transcrits Aiolos dans la LLC, indépendamment des marqueurs pronostiques (ZAP-70, statut mutationnel des IgVH). Cette augmentation, confirmée au niveau protéique, semble indépendante des niveaux d’H3K4me3 et H3K9ace.
| Type d'EPrint: | Thèse (Doctorat) |
|---|---|
| Directeur de Mémoire: | Rebollo, Angelita |
| Date: | 31 Octobre 2007 |
| Jury de Mémoire: | Meunier, Jean-Claude et Tonnelle, Cécile et Delic, Jozo et Merle-beral, Hélène et Rebollo, Angelita |
| Ecole Doctorale: | ED 435 AGRICULTURE, ALIMENTATION, BIOLOGIE, ENVIRONNEMENTS ET SANTE |
| Discipline: | Immunologie / Hématologie |
| Fonds: | AgroParistech |
| Institution: | AgroParistech |
| Laboratoire: | INSERM U543, Immunologie Cellulaire et Tissulaire |
| Sujets: | 7. Sciences de la vie et ingénierie du vivant |
| Mots-clés libres: | Hématopoïèse, Aiolos, épigénétique, Méthylation, Histones, Leucémie lymphoïde chronique, lymphome B, Transcription |
| Code ID: | 3066 |
| Déposé par : | Marianne DUHAMEL |
| Déposé le : | 05 Février 2008 |
Références Bibliographiques
Adams, C.C. and Workman, J.L. (1995) Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative. Mol Cell Biol, 15, 1405-1421.
Adkins, M.W., Howar, S.R. and Tyler, J.K. (2004) Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes. Mol Cell, 14, 657-666.
Adolfsson, J., Mansson, R., Buza-Vidas, N., Hultquist, A., Liuba, K., Jensen, C.T., Bryder, D., Yang, L., Borge, O.J., Thoren, L.A., Anderson, K., Sitnicka, E., Sasaki, Y., Sigvardsson, M. and Jacobsen, S.E. (2005) Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell, 121, 295-306.
Allsup, D.J., Kamiguti, A.S., Lin, K., Sherrington, P.D., Matrai, Z., Slupsky, J.R., Cawley, J.C. and Zuzel, M. (2005) B-cell receptor translocation to lipid rafts and associated signaling differ between prognostically important subgroups of chronic lymphocytic leukemia. Cancer Res, 65, 7328-7337.
Antequera, F. and Bird, A. (1993) Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci U S A, 90, 11995-11999.
Antica, M., Dubravcic, K., Weber, I., Raic, L., Labar, B. and Batinic, D. (2007) A search for a mutation of the Aiolos phosphorylation domain in lymphocytes from patients with leukemia. Haematologica, 92, 260-261.
Arney, K.L. and Fisher, A.G. (2004) Epigenetic aspects of differentiation. J Cell Sci, 117, 4355-4363.
Austen, B., Powell, J.E., Alvi, A., Edwards, I., Hooper, L., Starczynski, J., Taylor, A.M., Fegan, C., Moss, P. and Stankovic, T. (2005) Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood, 106, 3175-3182.
Avitahl, N., Winandy, S., Friedrich, C., Jones, B., Ge, Y. and Georgopoulos, K. (1999) Ikaros sets thresholds for T cell activation and regulates chromosome propagation. Immunity, 10, 333-343.
Bai, S., Ghoshal, K., Datta, J., Majumder, S., Yoon, S.O. and Jacob, S.T. (2005) DNA methyltransferase 3b regulates nerve growth factor-induced differentiation of PC12 cells by recruiting histone deacetylase 2. Mol Cell Biol, 25, 751-766.
Bain, G., Maandag, E.C., Izon, D.J., Amsen, D., Kruisbeek, A.M., Weintraub, B.C., Krop, I., Schlissel, M.S., Feeney, A.J., van Roon, M. and et al. (1994) E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell, 79, 885-892.
Bannister, A.J., Zegerman, P., Partridge, J.F., Miska, E.A., Thomas, J.O., Allshire, R.C. and Kouzarides, T. (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature, 410, 120-124.
Bea, S., Tort, F., Pinyol, M., Puig, X., Hernandez, L., Hernandez, S., Fernandez, P.L., van Lohuizen, M., Colomer, D. and Campo, E. (2001) BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res, 61, 2409-2412.
Bereshchenko, O.R., Gu, W. and Dalla-Favera, R. (2002) Acetylation inactivates the transcriptional repressor BCL6. Nat Genet, 32, 606-613.
Bergman, Y. and Cedar, H. (2004) A stepwise epigenetic process controls immunoglobulin allelic exclusion. Nat Rev Immunol, 4, 753-761.
Bernstein, B.E., Meissner, A. and Lander, E.S. (2007) The mammalian epigenome. Cell, 128, 669-681.
Bernstein, B.E., Mikkelsen, T.S., Xie, X., Kamal, M., Huebert, D.J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., Jaenisch, R., Wagschal, A., Feil, R., Schreiber, S.L. and Lander, E.S. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 125, 315-326.
Bertoni, F. and Ponzoni, M. (2007) The cellular origin of mantle cell lymphoma. Int J Biochem Cell Biol.
Bertoni, F. and Zucca, E. (2005) State-of-the-art therapeutics: marginal-zone lymphoma. J Clin Oncol, 23, 6415-6420.
Bestor, T.H. (1988) Cloning of a mammalian DNA methyltransferase. Gene, 74, 9-12.
Bestor, T.H. (1992) Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain. Embo J, 11, 2611-2617.
Binet, J.L., Auquier, A., Dighiero, G., Chastang, C., Piguet, H., Goasguen, J., Vaugier, G., Potron, G., Colona, P., Oberling, F., Thomas, M., Tchernia, G., Jacquillat, C., Boivin, P., Lesty, C., Duault, M.T., Monconduit, M., Belabbes, S. and Gremy, F. (1981) A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer, 48, 198-206.
Bird, A. (2002) DNA methylation patterns and epigenetic memory. Genes Dev, 16, 6-21.
Bird, A.P., Taggart, M.H., Nicholls, R.D. and Higgs, D.R. (1987) Non-methylated CpG-rich islands at the human alpha-globin locus: implications for evolution of the alpha-globin pseudogene. Embo J, 6, 999-1004.
Boeger, H., Griesenbeck, J., Strattan, J.S. and Kornberg, R.D. (2004) Removal of promoter nucleosomes by disassembly rather than sliding in vivo. Mol Cell, 14, 667-673.
Bosselut, R. (2004) CD4/CD8-lineage differentiation in the thymus: from nuclear effectors to membrane signals. Nat Rev Immunol, 4, 529-540.
Brendolan, A., Rosado, M.M., Carsetti, R., Selleri, L. and Dear, T.N. (2007) Development and function of the mammalian spleen. Bioessays, 29, 166-177.
Brown, K.E., Baxter, J., Graf, D., Merkenschlager, M. and Fisher, A.G. (1999) Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol Cell, 3, 207-217.
Brown, K.E., Guest, S.S., Smale, S.T., Hahm, K., Merkenschlager, M. and Fisher, A.G. (1997) Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell, 91, 845-854.
Bruniquel, D. and Schwartz, R.H. (2003) Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol, 4, 235-240.
Bucceri, A., Kapitza, K. and Thoma, F. (2006) Rapid accessibility of nucleosomal DNA in yeast on a second time scale. Embo J, 25, 3123-3132.
Byrd, J.C., Marcucci, G., Parthun, M.R., Xiao, J.J., Klisovic, R.B., Moran, M., Lin, T.S., Liu, S., Sklenar, A.R., Davis, M.E., Lucas, D.M., Fischer, B., Shank, R., Tejaswi, S.L., Binkley, P., Wright, J., Chan, K.K. and Grever, M.R. (2005) A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood, 105, 959-967.
Caballero, R., Setien, F., Lopez-Serra, L., Boix-Chornet, M., Fraga, M.F., Ropero, S., Megias, D., Alaminos, M., Sanchez-Tapia, E.M., Montoya, M.C., Esteller, M., Gonzalez-Sarmiento, R. and Ballestar, E. (2007) Combinatorial effects of splice variants modulate function of Aiolos. J Cell Sci, 120, 2619-2630.
Calin, G.A., Ferracin, M., Cimmino, A., Di Leva, G., Shimizu, M., Wojcik, S.E., Iorio, M.V., Visone, R., Sever, N.I., Fabbri, M., Iuliano, R., Palumbo, T., Pichiorri, F., Roldo, C., Garzon, R., Sevignani, C., Rassenti, L., Alder, H., Volinia, S., Liu, C.G., Kipps, T.J., Negrini, M. and Croce, C.M. (2005) A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med, 353, 1793-1801.
Cameron, E.E., Bachman, K.E., Myohanen, S., Herman, J.G. and Baylin, S.B. (1999) Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet, 21, 103-107.
Campanero, M.R., Armstrong, M.I. and Flemington, E.K. (2000) CpG methylation as a mechanism for the regulation of E2F activity. Proc Natl Acad Sci U S A, 97, 6481-6486.
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.
Cariappa, A., Kim, T.J. and Pillai, S. (1999) Accelerated emigration of B lymphocytes in the Xid mouse. J Immunol, 162, 4417-4423.
Cariappa, A., Liou, H.C., Horwitz, B.H. and Pillai, S. (2000) Nuclear factor kappa B is required for the development of marginal zone B lymphocytes. J Exp Med, 192, 1175-1182.
Cariappa, A., Tang, M., Parng, C., Nebelitskiy, E., Carroll, M., Georgopoulos, K. and Pillai, S. (2001) The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21. Immunity, 14, 603-615.
Carsetti, R., Rosado, M.M. and Wardmann, H. (2004) Peripheral development of B cells in mouse and man. Immunol Rev, 197, 179-191.
Cattoretti, G., Chang, C.C., Cechova, K., Zhang, J., Ye, B.H., Falini, B., Louie, D.C., Offit, K., Chaganti, R.S. and Dalla-Favera, R. (1995) BCL-6 protein is expressed in germinal-center B cells. Blood, 86, 45-53.
Chang, C.C., Lorek, J., Sabath, D.E., Li, Y., Chitambar, C.R., Logan, B., Kampalath, B. and Cleveland, R.P. (2002) Expression of MUM1/IRF4 correlates with clinical outcome in patients with B-cell chronic lymphocytic leukemia. Blood, 100, 4671-4675.
Chen, L., Widhopf, G., Huynh, L., Rassenti, L., Rai, K.R., Weiss, A. and Kipps, T.J. (2002) Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood, 100, 4609-4614.
Cheung, P., Tanner, K.G., Cheung, W.L., Sassone-Corsi, P., Denu, J.M. and Allis, C.D. (2000) Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Mol Cell, 5, 905-915.
Chiorazzi, N., Rai, K.R. and Ferrarini, M. (2005) Chronic lymphocytic leukemia. N Engl J Med, 352, 804-815.
Cimmino, A., Calin, G.A., Fabbri, M., Iorio, M.V., Ferracin, M., Shimizu, M., Wojcik, S.E., Aqeilan, R.I., Zupo, S., Dono, M., Rassenti, L., Alder, H., Volinia, S., Liu, C.G., Kipps, T.J., Negrini, M. and Croce, C.M. (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A, 102, 13944-13949.
Cobb, B.S., Morales-Alcelay, S., Kleiger, G., Brown, K.E., Fisher, A.G. and Smale, S.T. (2000) Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding. Genes Dev, 14, 2146-2160.
Corcoran, L.M. and Karvelas, M. (1994) Oct-2 is required early in T cell-independent B cell activation for G1 progression and for proliferation. Immunity, 1, 635-645.
Cortes, M. and Georgopoulos, K. (2004) Aiolos is required for the generation of high affinity bone marrow plasma cells responsible for long-term immunity. J Exp Med, 199, 209-219.
Cragg, M.S., Chan, H.T., Fox, M.D., Tutt, A., Smith, A., Oscier, D.G., Hamblin, T.J. and Glennie, M.J. (2002) The alternative transcript of CD79b is overexpressed in B-CLL and inhibits signaling for apoptosis. Blood, 100, 3068-3076.
Crespo, M., Bosch, F., Villamor, N., Bellosillo, B., Colomer, D., Rozman, M., Marce, S., Lopez-Guillermo, A., Campo, E. and Montserrat, E. (2003) ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med, 348, 1764-1775.
Cuthbert, G.L., Daujat, S., Snowden, A.W., Erdjument-Bromage, H., Hagiwara, T., Yamada, M., Schneider, R., Gregory, P.D., Tempst, P., Bannister, A.J. and Kouzarides, T. (2004) Histone deimination antagonizes arginine methylation. Cell, 118, 545-553.
Czermin, B., Schotta, G., Hulsmann, B.B., Brehm, A., Becker, P.B., Reuter, G. and Imhof, A. (2001) Physical and functional association of SU(VAR)3-9 and HDAC1 in Drosophila. EMBO Rep, 2, 915-919.
Damle, R.N., Batliwalla, F.M., Ghiotto, F., Valetto, A., Albesiano, E., Sison, C., Allen, S.L., Kolitz, J., Vinciguerra, V.P., Kudalkar, P., Wasil, T., Rai, K.R., Ferrarini, M., Gregersen, P.K. and Chiorazzi, N. (2004) Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. Blood, 103, 375-382.
Damle, R.N., Wasil, T., Fais, F., Ghiotto, F., Valetto, A., Allen, S.L., Buchbinder, A., Budman, D., Dittmar, K., Kolitz, J., Lichtman, S.M., Schulman, P., Vinciguerra, V.P., Rai, K.R., Ferrarini, M. and Chiorazzi, N. (1999) Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood, 94, 1840-1847.
de Jong, D. (2005) Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors. J Clin Oncol, 23, 6358-6363.
De Smet, C., Lurquin, C., Lethe, B., Martelange, V. and Boon, T. (1999) DNA methylation is the primary silencing mechanism for a set of germ line- and tumor-specific genes with a CpG-rich promoter. Mol Cell Biol, 19, 7327-7335.
Deaglio, S., Vaisitti, T., Aydin, S., Ferrero, E. and Malavasi, F. (2006) In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia. Blood, 108, 1135-1144.
DeKoter, R.P., Lee, H.J. and Singh, H. (2002) PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors. Immunity, 16, 297-309.
DeKoter, R.P. and Singh, H. (2000) Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science, 288, 1439-1441.
DeKoter, R.P., Walsh, J.C. and Singh, H. (1998) PU.1 regulates both cytokine-dependent proliferation and differentiation of granulocyte/macrophage progenitors. Embo J, 17, 4456-4468.
Del Poeta, G., Maurillo, L., Venditti, A., Buccisano, F., Epiceno, A.M., Capelli, G., Tamburini, A., Suppo, G., Battaglia, A., Del Principe, M.I., Del Moro, B., Masi, M. and Amadori, S. (2001) Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood, 98, 2633-2639.
Deltour, S., Chopin, V. and Leprince, D. (2005) [Epigenetics and cancer]. Med Sci (Paris), 21, 405-411.
Dent, A.L., Shaffer, A.L., Yu, X., Allman, D. and Staudt, L.M. (1997) Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science, 276, 589-592.
Dhalluin, C., Carlson, J.E., Zeng, L., He, C., Aggarwal, A.K. and Zhou, M.M. (1999) Structure and ligand of a histone acetyltransferase bromodomain. Nature, 399, 491-496.
Dohner, H., Fischer, K., Bentz, M., Hansen, K., Benner, A., Cabot, G., Diehl, D., Schlenk, R., Coy, J., Stilgenbauer, S. and et al. (1995) p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood, 85, 1580-1589.
Dohner, H., Stilgenbauer, S., Benner, A., Leupolt, E., Krober, A., Bullinger, L., Dohner, K., Bentz, M. and Lichter, P. (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med, 343, 1910-1916.
Dovat, S., Ronni, T., Russell, D., Ferrini, R., Cobb, B.S. and Smale, S.T. (2002) A common mechanism for mitotic inactivation of C2H2 zinc finger DNA-binding domains. Genes Dev, 16, 2985-2990.
Duhamel, M., Navarro, P., Cario-André, M., Rebollo, A. (2007) Differential epigenetic regulation of Aiolos expression in human tumoral cell lines and primary cells. Submitted.
Duhamel, M., Arrouss, I., Merle-Béral, H., Rebollo, A. (2007) The Aiolos transcription factor is up-regulated in chronic lymphocytic leukemia. Submitted.
Dumortier, A., Jeannet, R., Kirstetter, P., Kleinmann, E., Sellars, M., dos Santos, N.R., Thibault, C., Barths, J., Ghysdael, J., Punt, J.A., Kastner, P. and Chan, S. (2006) Notch activation is an early and critical event during T-Cell leukemogenesis in Ikaros-deficient mice. Mol Cell Biol, 26, 209-220.
Dumortier, A., Kirstetter, P., Kastner, P. and Chan, S. (2003) Ikaros regulates neutrophil differentiation. Blood, 101, 2219-2226.
El-Osta, A., Kantharidis, P., Zalcberg, J.R. and Wolffe, A.P. (2002) Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation. Mol Cell Biol, 22, 1844-1857.
Ernst, P., Hahm, K. and Smale, S.T. (1993) Both LyF-1 and an Ets protein interact with a critical promoter element in the murine terminal transferase gene. Mol Cell Biol, 13, 2982-2992.
Ernst, P., Hahm, K., Trinh, L., Davis, J.N., Roussel, M.F., Turck, C.W. and Smale, S.T. (1996) A potential role for Elf-1 in terminal transferase gene regulation. Mol Cell Biol, 16, 6121-6131.
Fais, F., Ghiotto, F., Hashimoto, S., Sellars, B., Valetto, A., Allen, S.L., Schulman, P., Vinciguerra, V.P., Rai, K., Rassenti, L.Z., Kipps, T.J., Dighiero, G., Schroeder, H.W., Jr., Ferrarini, M. and Chiorazzi, N. (1998) Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest, 102, 1515-1525.
Feinberg, A.P. and Tycko, B. (2004) The history of cancer epigenetics. Nat Rev Cancer, 4, 143-153.
Feng, Q., Wang, H., Ng, H.H., Erdjument-Bromage, H., Tempst, P., Struhl, K. and Zhang, Y. (2002) Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr Biol, 12, 1052-1058.
Fernandez, V., Hartmann, E., Ott, G., Campo, E. and Rosenwald, A. (2005) Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways. J Clin Oncol, 23, 6364-6369.
Ferrer, A., Ollila, J., Tobin, G., Nagy, B., Thunberg, U., Aalto, Y., Vihinen, M., Vilpo, J., Rosenquist, R. and Knuutila, S. (2004) Different gene expression in immunoglobulin-mutated and immunoglobulin-unmutated forms of chronic lymphocytic leukemia. Cancer Genet Cytogenet, 153, 69-72.
Fraga, M.F., Ballestar, E., Villar-Garea, A., Boix-Chornet, M., Espada, J., Schotta, G., Bonaldi, T., Haydon, C., Ropero, S., Petrie, K., Iyer, N.G., Perez-Rosado, A., Calvo, E., Lopez, J.A., Cano, A., Calasanz, M.J., Colomer, D., Piris, M.A., Ahn, N., Imhof, A., Caldas, C., Jenuwein, T. and Esteller, M. (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet, 37, 391-400.
Franco, V., Florena, A.M. and Iannitto, E. (2003) Splenic marginal zone lymphoma. Blood, 101, 2464-2472.
Fujita, N., Watanabe, S., Ichimura, T., Tsuruzoe, S., Shinkai, Y., Tachibana, M., Chiba, T. and Nakao, M. (2003) Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem, 278, 24132-24138.
Fuks, F., Burgers, W.A., Brehm, A., Hughes-Davies, L. and Kouzarides, T. (2000) DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat Genet, 24, 88-91.
Fuks, F., Burgers, W.A., Godin, N., Kasai, M. and Kouzarides, T. (2001) Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. Embo J, 20, 2536-2544.
Fuks, F., Hurd, P.J., Deplus, R. and Kouzarides, T. (2003a) The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res, 31, 2305-2312.
Fuks, F., Hurd, P.J., Wolf, D., Nan, X., Bird, A.P. and Kouzarides, T. (2003b) The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem, 278, 4035-4040.
Furman, R.R., Asgary, Z., Mascarenhas, J.O., Liou, H.C. and Schattner, E.J. (2000) Modulation of NF-kappa B activity and apoptosis in chronic lymphocytic leukemia B cells. J Immunol, 164, 2200-2206.
Fuxa, M., Skok, J., Souabni, A., Salvagiotto, G., Roldan, E. and Busslinger, M. (2004) Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes Dev, 18, 411-422.
Galm, O., Herman, J.G. and Baylin, S.B. (2006) The fundamental role of epigenetics in hematopoietic malignancies. Blood Rev, 20, 1-13.
Gardiner-Garden, M. and Frommer, M. (1987) CpG islands in vertebrate genomes. J Mol Biol, 196, 261-282.
Ge, Y.Z., Pu, M.T., Gowher, H., Wu, H.P., Ding, J.P., Jeltsch, A. and Xu, G.L. (2004) Chromatin targeting of de novo DNA methyltransferases by the PWWP domain. J Biol Chem, 279, 25447-25454.
Georgopoulos, K., Bigby, M., Wang, J.H., Molnar, A., Wu, P., Winandy, S. and Sharpe, A. (1994) The Ikaros gene is required for the development of all lymphoid lineages. Cell, 79, 143-156.
Georgopoulos, K., Moore, D.D. and Derfler, B. (1992) Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science, 258, 808-812.
Ghadiri, A., Duhamel, M., Fleischer, A., Reimann, A., Dessauge, F. and Rebollo, A. (2007) Critical function of Ikaros in controlling Aiolos gene expression. FEBS Lett, 581, 1605-1616.
Ghoshal, K., Datta, J., Majumder, S., Bai, S., Kutay, H., Motiwala, T. and Jacob, S.T. (2005) 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Mol Cell Biol, 25, 4727-4741.
Ghoshal, K., Majumder, S. and Jacob, S.T. (2002) Analysis of promoter methylation and its role in silencing metallothionein I gene expression in tumor cells. Methods Enzymol, 353, 476-486.
Goldberg, A.D., Allis, C.D. and Bernstein, E. (2007) Epigenetics: a landscape takes shape. Cell, 128, 635-638.
Goldmit, M., Ji, Y., Skok, J., Roldan, E., Jung, S., Cedar, H. and Bergman, Y. (2005) Epigenetic ontogeny of the Igk locus during B cell development. Nat Immunol, 6, 198-203.
Goll, M.G. and Bestor, T.H. (2005) Eukaryotic cytosine methyltransferases. Annu Rev Biochem, 74, 481-514.
Gomez-del Arco, P., Koipally, J. and Georgopoulos, K. (2005) Ikaros SUMOylation: switching out of repression. Mol Cell Biol, 25, 2688-2697.
Gomez-del Arco, P., Maki, K. and Georgopoulos, K. (2004) Phosphorylation controls Ikaros's ability to negatively regulate the G(1)-S transition. Mol Cell Biol, 24, 2797-2807.
Grabowski, P., Hultdin, M., Karlsson, K., Tobin, G., Aleskog, A., Thunberg, U., Laurell, A., Sundstrom, C., Rosenquist, R. and Roos, G. (2005) Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood, 105, 4807-4812.
Gregoretti, I.V., Lee, Y.M. and Goodson, H.V. (2004) Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol, 338, 17-31.
Grozinger, C.M. and Schreiber, S.L. (2000) Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization. Proc Natl Acad Sci U S A, 97, 7835-7840.
Guipaud, O., Deriano, L., Salin, H., Vallat, L., Sabatier, L., Merle-Beral, H. and Delic, J. (2003) B-cell chronic lymphocytic leukaemia: a polymorphic family unified by genomic features. Lancet Oncol, 4, 505-514.
Hahm, K., Cobb, B.S., McCarty, A.S., Brown, K.E., Klug, C.A., Lee, R., Akashi, K., Weissman, I.L., Fisher, A.G. and Smale, S.T. (1998) Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin. Genes Dev, 12, 782-796.
Hahm, K., Ernst, P., Lo, K., Kim, G.S., Turck, C. and Smale, S.T. (1994) The lymphoid transcription factor LyF-1 is encoded by specific, alternatively spliced mRNAs derived from the Ikaros gene. Mol Cell Biol, 14, 7111-7123.
Haire, R.N., Miracle, A.L., Rast, J.P. and Litman, G.W. (2000) Members of the Ikaros gene family are present in early representative vertebrates. J Immunol, 165, 306-312.
Hamblin, T.J., Davis, Z., Gardiner, A., Oscier, D.G. and Stevenson, F.K. (1999) Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood, 94, 1848-1854.
Hanada, M., Delia, D., Aiello, A., Stadtmauer, E. and Reed, J.C. (1993) bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood, 82, 1820-1828.
Hark, A.T., Schoenherr, C.J., Katz, D.J., Ingram, R.S., Levorse, J.M. and Tilghman, S.M. (2000) CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature, 405, 486-489.
Harker, N., Naito, T., Cortes, M., Hostert, A., Hirschberg, S., Tolaini, M., Roderick, K., Georgopoulos, K. and Kioussis, D. (2002) The CD8alpha gene locus is regulated by the Ikaros family of proteins. Mol Cell, 10, 1403-1415.
Harris, M.B., Chang, C.C., Berton, M.T., Danial, N.N., Zhang, J., Kuehner, D., Ye, B.H., Kvatyuk, M., Pandolfi, P.P., Cattoretti, G., Dalla-Favera, R. and Rothman, P.B. (1999) Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching. Mol Cell Biol, 19, 7264-7275.
Hassan, A.H., Neely, K.E. and Workman, J.L. (2001) Histone acetyltransferase complexes stabilize swi/snf binding to promoter nucleosomes. Cell, 104, 817-827.
Hong, W., Kim, A.Y., Ky, S., Rakowski, C., Seo, S.B., Chakravarti, D., Atchison, M. and Blobel, G.A. (2002) Inhibition of CBP-mediated protein acetylation by the Ets family oncoprotein PU.1. Mol Cell Biol, 22, 3729-3743.
Hosokawa, Y., Maeda, Y., Ichinohasama, R., Miura, I., Taniwaki, M. and Seto, M. (2000) The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma. Blood, 95, 2719-2721.
Hosokawa, Y., Maeda, Y., Takahashi, E., Suzuki, M. and Seto, M. (1999) Human aiolos, an ikaros-related zinc finger DNA binding protein: cDNA cloning, tissue expression pattern, and chromosomal mapping. Genomics, 61, 326-329.
Humbert, P.O. and Corcoran, L.M. (1997) oct-2 gene disruption eliminates the peritoneal B-1 lymphocyte lineage and attenuates B-2 cell maturation and function. J Immunol, 159, 5273-5284.
Huyen, Y., Zgheib, O., Ditullio, R.A., Jr., Gorgoulis, V.G., Zacharatos, P., Petty, T.J., Sheston, E.A., Mellert, H.S., Stavridi, E.S. and Halazonetis, T.D. (2004) Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature, 432, 406-411.
Ibrahim, S., Keating, M., Do, K.A., O'Brien, S., Huh, Y.O., Jilani, I., Lerner, S., Kantarjian, H.M. and Albitar, M. (2001) CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia. Blood, 98, 181-186.
Insinga, A., Monestiroli, S., Ronzoni, S., Carbone, R., Pearson, M., Pruneri, G., Viale, G., Appella, E., Pelicci, P. and Minucci, S. (2004) Impairment of p53 acetylation, stability and function by an oncogenic transcription factor. Embo J, 23, 1144-1154.
Issa, J.P., Kantarjian, H., Mohan, A., O'Brien, S., Cortes, J., Pierce, S. and Talpaz, M. (1999) Methylation of the ABL1 promoter in chronic myelogenous leukemia: lack of prognostic significance. Blood, 93, 2075-2080.
Iwakoshi, N.N., Lee, A.H. and Glimcher, L.H. (2003) The X-box binding protein-1 transcription factor is required for plasma cell differentiation and the unfolded protein response. Immunol Rev, 194, 29-38.
Jenuwein, T. and Allis, C.D. (2001) Translating the histone code. Science, 293, 1074-1080.
Jones, P.A. (2002) DNA methylation and cancer. Oncogene, 21, 5358-5360.
Jones, P.A. and Baylin, S.B. (2007) The epigenomics of cancer. Cell, 128, 683-692.
Joshi, A.A. and Struhl, K. (2005) Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol Cell, 20, 971-978.
Kamakaka, R.T. and Biggins, S. (2005) Histone variants: deviants? Genes Dev, 19, 295-310.
Karray, S., Merle-Beral, H., Vazquez, A., Gerard, J.P., Debre, P. and Galanaud, P. (1987) Functional heterogeneity of B-CLL lymphocytes: dissociated responsiveness to growth factors and distinct requirements for a first activation signal. Blood, 70, 1105-1110.
Kaufmann, C., Yoshida, T., Perotti, E.A., Landhuis, E., Wu, P. and Georgopoulos, K. (2003) A complex network of regulatory elements in Ikaros and their activity during hemo-lymphopoiesis. Embo J, 22, 2211-2223.
Kee, B.L. and Murre, C. (1998) Induction of early B cell factor (EBF) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12. J Exp Med, 188, 699-713.
Kelley, C.M., Ikeda, T., Koipally, J., Avitahl, N., Wu, L., Georgopoulos, K. and Morgan, B.A. (1998) Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors. Curr Biol, 8, 508-515.
Khan, W.N., Alt, F.W., Gerstein, R.M., Malynn, B.A., Larsson, I., Rathbun, G., Davidson, L., Muller, S., Kantor, A.B., Herzenberg, L.A. and et al. (1995) Defective B cell development and function in Btk-deficient mice. Immunity, 3, 283-299.
Kim, J., Sif, S., Jones, B., Jackson, A., Koipally, J., Heller, E., Winandy, S., Viel, A., Sawyer, A., Ikeda, T., Kingston, R. and Georgopoulos, K. (1999) Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity, 10, 345-355.
Kim, U., Qin, X.F., Gong, S., Stevens, S., Luo, Y., Nussenzweig, M. and Roeder, R.G. (1996) The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes. Nature, 383, 542-547.
Kioussis, D. and Ellmeier, W. (2002) Chromatin and CD4, CD8A and CD8B gene expression during thymic differentiation. Nat Rev Immunol, 2, 909-919.
Kirmizis, A., Bartley, S.M., Kuzmichev, A., Margueron, R., Reinberg, D., Green, R. and Farnham, P.J. (2004) Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes Dev, 18, 1592-1605.
Kirstetter, P., Thomas, M., Dierich, A., Kastner, P. and Chan, S. (2002) Ikaros is critical for B cell differentiation and function. Eur J Immunol, 32, 720-730.
Klein, U., Tu, Y., Stolovitzky, G.A., Mattioli, M., Cattoretti, G., Husson, H., Freedman, A., Inghirami, G., Cro, L., Baldini, L., Neri, A., Califano, A. and Dalla-Favera, R. (2001) Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J Exp Med, 194, 1625-1638.
Klemsz, M.J., McKercher, S.R., Celada, A., Van Beveren, C. and Maki, R.A. (1990) The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell, 61, 113-124.
Klose, R.J. and Bird, A.P. (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci, 31, 89-97.
Klose, R.J., Kallin, E.M. and Zhang, Y. (2006) JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet, 7, 715-727.
Klug, C.A., Morrison, S.J., Masek, M., Hahm, K., Smale, S.T. and Weissman, I.L. (1998) Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proc Natl Acad Sci U S A, 95, 657-662.
Kohonen, P., Nera, K.P. and Lassila, O. (2004) Avian Helios and evolution of the Ikaros family. Scand J Immunol, 60, 100-107.
Koipally, J. and Georgopoulos, K. (2000) Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity. J Biol Chem, 275, 19594-19602.
Koipally, J. and Georgopoulos, K. (2002a) Ikaros-CtIP interactions do not require C-terminal binding protein and participate in a deacetylase-independent mode of repression. J Biol Chem, 277, 23143-23149.
Koipally, J. and Georgopoulos, K. (2002b) A molecular dissection of the repression circuitry of Ikaros. J Biol Chem, 277, 27697-27705.
Koipally, J., Heller, E.J., Seavitt, J.R. and Georgopoulos, K. (2002) Unconventional potentiation of gene expression by Ikaros. J Biol Chem, 277, 13007-13015.
Koipally, J., Renold, A., Kim, J. and Georg