Generic placeholder image

Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

Targeting Chromatin Remodeling for Cancer Therapy

Author(s): Jasmine Kaur, Abdelkader Daoud and Scott T. Eblen*

Volume 12, Issue 3, 2019

Page: [215 - 229] Pages: 15

DOI: 10.2174/1874467212666190215112915

Abstract

Background: Epigenetic alterations comprise key regulatory events that dynamically alter gene expression and their deregulation is commonly linked to the pathogenesis of various diseases, including cancer. Unlike DNA mutations, epigenetic alterations involve modifications to proteins and nucleic acids that regulate chromatin structure without affecting the underlying DNA sequence, altering the accessibility of the transcriptional machinery to the DNA, thus modulating gene expression. In cancer cells, this often involves the silencing of tumor suppressor genes or the increased expression of genes involved in oncogenesis. Advances in laboratory medicine have made it possible to map critical epigenetic events, including histone modifications and DNA methylation, on a genome-wide scale. Like the identification of genetic mutations, mapping of changes to the epigenetic landscape has increased our understanding of cancer progression. However, in contrast to irreversible genetic mutations, epigenetic modifications are flexible and dynamic, thereby making them promising therapeutic targets. Ongoing studies are evaluating the use of epigenetic drugs in chemotherapy sensitization and immune system modulation. With the preclinical success of drugs that modify epigenetics, along with the FDA approval of epigenetic drugs including the DNA methyltransferase 1 (DNMT1) inhibitor 5-azacitidine and the histone deacetylase (HDAC) inhibitor vorinostat, there has been a rise in the number of drugs that target epigenetic modulators over recent years.

Conclusion: We provide an overview of epigenetic modulations, particularly those involved in cancer, and discuss the recent advances in drug development that target these chromatin-modifying events, primarily focusing on novel strategies to regulate the epigenome.

Keywords: Epigenetics, chromatin, cancer, methylation, acetylation, histones, DNA.

Graphical Abstract
[1]
Morgan, M.A.; Shilatifard, A. Chromatin signatures of cancer. Genes Dev., 2015, 29, 238-249.
[2]
Kornberg, R.D. Chromatin structure: A repeating unit of histones and DNA. Science, 1974, 184, 868-871.
[3]
Laybourn, P.J.; Kadonaga, J.T. Role of nucleosomal cores and histone H1 in regulation of transcription by RNA polymerase II. Science, 1991, 254, 238-245.
[4]
Cutter, A.R.; Hayes, J.J. Linker histones: Novel insights into structure-specific recognition of the nucleosome. Biochem. Cell Biol., 2016, 95, 171-178.
[5]
Campos, E.I.; Reinberg, D. Histones: Annotating chromatin. Annu. Rev. Genet., 2009, 43, 559-599.
[6]
Campos, E.I.; Reinberg, D. New chaps in the histone chaperone arena. Genes Dev., 2010, 24, 1334-1338.
[7]
Lai, W.K.; Pugh, B.F. Understanding nucleosome dynamics and their links to gene expression and DNA replication. Nat. Rev. Mol. Cell Biol., 2017, 18, 548.
[8]
Biswas, S.; Rao, C.M. Epigenetic tools (the writers, the readers and the erasers) and their implications in cancer therapy. Eur. J. Pharmacol., 2018, 837, 8-24.
[9]
Kadoch, C.; Crabtree, G.R. Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics. Science Adv., 2015, 1e1500447
[10]
Verma, M.; Kumar, V. Epigenetic drugs for cancer and precision medicine. In Epigenetics Aging Longevity; Elsevier, 2018, pp. 439-451.
[11]
Dawson, M.A. The cancer epigenome: Concepts, challenges, and therapeutic opportunities. Science, 2017, 355, 1147-1152.
[12]
Shen, H.; Laird, P.W. Interplay between the cancer genome and epigenome. Cell, 2013, 153, 38-55.
[13]
Suvà, M.L.; Riggi, N.; Bernstein, B.E. Epigenetic reprogramming in cancer. Science, 2013, 339, 1567-1570.
[14]
Piunti, A.; Shilatifard, A. Epigenetic balance of gene expression by polycomb and compass families. Science, 2016, 352(6290)aad9780
[15]
Barski, A.; Cuddapah, S.; Cui, K.; Roh, T.Y.; Schones, D.E.; Wang, Z.; Wei, G.; Chepelev, I.; Zhao, K. High-resolution profiling of histone methylations in the human genome. Cell, 2007, 129, 823-837.
[16]
Ziemin-van der Poel, S.; McCabe, N.R.; Gill, H.J.; Espinosa, R.; Patel, Y.; Harden, A.; Rubinelli, P.; Smith, S.D.; LeBeau, M.M.; Rowley, J.D. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc. Natl. Acad. Sci. USA, 1991, 88, 10735-10739.
[17]
Morin, R.D.; Mendez-Lago, M.; Mungall, A.J.; Goya, R.; Mungall, K.L.; Corbett, R.D.; Johnson, N.A.; Severson, T.M.; Chiu, R.; Field, M. Frequent mutation of histone-modifying genes in non-hodgkin lymphoma. Nature, 2011, 476, 298-303.
[18]
Sneeringer, C.J.; Scott, M.P.; Kuntz, K.W.; Knutson, S.K.; Pollock, R.M.; Richon, V.M.; Copeland, R.A. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc. Natl. Acad. Sci. USA, 2010, 107, 20980-20985.
[19]
Yap, D.B.; Chu, J.; Berg, T.; Schapira, M.; Cheng, S.W.; Moradian, A.; Morin, R.D.; Mungall, A.J.; Meissner, B.; Boyle, M.; Marquez, V.E.; Marra, M.A.; Gascoyne, R.D.; Humphries, R.K.; Arrowsmith, C.H.; Morin, G.B.; Aparicio, S.A. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood, 2011, 117, 2451-2459.
[20]
McCabe, M.T.; Graves, A.P.; Ganji, G.; Diaz, E.; Halsey, W.S.; Jiang, Y.; Smitheman, K.N.; Ott, H.M.; Pappalardi, M.B.; Allen, K.E. Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27). Proc. Natl. Acad. Sci. USA, 2012, 109, 2989-2994.
[21]
Ott, H.M.; Graves, A.; Pappalardi, M.B.; Huddleston, M.; Halsey, W.S.; Hughes, A.; Groy, A.; Dul, E.; Jiang, Y.; Bai, Y. A687V EZH2 is a driver of histone H3 lysine 27 (H3K27) hyper-trimethylation. Mol. Cancer Ther., 2014, 13, 3062-3073.
[22]
McCabe, M.T.; Ott, H.M.; Ganji, G.; Korenchuk, S.; Thompson, C.; Van Aller, G.S.; Liu, Y.; Graves, A.P.; Diaz, E.; LaFrance, L.V. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 2012, 492, 108-112.
[23]
Taplin, M-E.; Hussain, A.; Shore, N.D.; Bradley, B.; Trojer, P.; Lebedinsky, C.; Senderowicz, A.M.; Antonarakis, E.S. A phase 1b/2 study of CPI-1205, a small molecule inhibitor of EZH2, combined with enzalutamide (E) or abiraterone/prednisone (A/P) in patients with metastatic castration resistant prostate cancer (mCRPC). J. Clin. Oncol., 2018, 36, s6.
[24]
Italiano, A.; Soria, J-C.; Toulmonde, M.; Michot, J-M.; Lucchesi, C.; Varga, A.; Coindre, J-M.; Blakemore, S.J.; Clawson, A.; Suttle, B. Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-hodgkin lymphoma and advanced solid tumours: A first-in-human, open-label, phase 1 study. Lancet Oncol., 2018, 19, 649-659.
[25]
Schwartzentruber, J.; Korshunov, A.; Liu, X-Y.; Jones, D.T.; Pfaff, E.; Jacob, K.; Sturm, D.; Fontebasso, A.M.; Quang, D-A.K.; Tönjes, M. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature, 2012, 482, 226-231.
[26]
Venneti, S.; Garimella, M.T.; Sullivan, L.M.; Martinez, D.; Huse, J.T.; Heguy, A.; Santi, M.; Thompson, C.B.; Judkins, A.R. Evaluation of h istone 3 lysine 27 trimethylation (H3K27me3) and enhancer of zest 2 (EZH 2) in pediatric glial and glioneuronal tumors shows decreased H3K27me3 in H3F3a K27M mutant glioblastomas. Brain Pathol., 2013, 23, 558-564.
[27]
Lewis, P.W.; Müller, M. Koletsky, M.; Cordero, F.; Lin, S.; Banaszynski, L.; Garcia, B. A.; Muir, T.; Becher, O.; Allis, C. D. Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science, 2013, 340, 857-861.
[28]
Li, H.; Kaminski, M.S.; Li, Y.; Yildiz, M.; Ouillette, P.; Jones, S.; Fox, H.; Jacobi, K.; Saiya-Cork, K.; Bixby, D.; Lebovic, D.; Roulston, D.; Shedden, K.; Sabel, M.; Marentette, L.; Cimmino, V.; Chang, A.E.; Malek, S.N. Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma. Blood, 2014, 123, 1487-1498.
[29]
Goll, M.G.; Kirpekar, F.; Maggert, K.A.; Yoder, J.A.; Hsieh, C-L.; Zhang, X.; Golic, K.G.; Jacobsen, S.E.; Bestor, T.H. Methylation of tRNAAsp by the DNA methyltransferase homolog DNMT2. Science, 2006, 311, 395-398.
[30]
Schubeler, D. Function and information content of DNA methylation. Nature, 2015, 517, 321-326.
[31]
Tahiliani, M.; Koh, K.P.; Shen, Y.; Pastor, W.A.; Bandukwala, H.; Brudno, Y.; Agarwal, S.; Iyer, L.M.; Liu, D.R.; Aravind, L. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science, 2009, 324, 930-935.
[32]
Branco, M.R.; Ficz, G.; Reik, W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat. Rev. Genet., 2011, 13, 7-13.
[33]
Lister, R.; Pelizzola, M.; Dowen, R.H.; Hawkins, R.D.; Hon, G.; Tonti-Filippini, J.; Nery, J.R.; Lee, L.; Ye, Z.; Ngo, Q-M. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature, 2009, 462, 315-322.
[34]
Stefansson, O.A.; Moran, S.; Gomez, A.; Sayols, S.; Arribas-Jorba, C.; Sandoval, J.; Hilmarsdottir, H.; Olafsdottir, E.; Tryggvadottir, L.; Jonasson, J.G. A DNA methylation‐based definition of biologically distinct breast cancer subtypes. Mol. Oncol., 2015, 9, 555-568.
[35]
Herman, J.G.; Umar, A.; Polyak, K.; Graff, J.R.; Ahuja, N.; Issa, J.P.; Markowitz, S.; Willson, J.K.; Hamilton, S.R.; Kinzler, K.W.; Kane, M.F.; Kolodner, R.D.; Vogelstein, B.; Kunkel, T.A.; Baylin, S.B. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc. Natl. Acad. Sci. U S A., , 1998, 95, 6870-6875.
[36]
Wajed, S.A.; Laird, P.W.; DeMeester, T.R. DNA methylation: An alternative pathway to cancer. Ann. Surg., 2001, 234, 10-20.
[37]
Pistore, C.; Giannoni, E.; Colangelo, T.; Rizzo, F.; Magnani, E.; Muccillo, L.; Giurato, G.; Mancini, M.; Rizzo, S.; Riccardi, M. DNA methylation variations are required for epithelial-to-mesenchymal transition induced by cancer-associated fibroblasts in prostate cancer cells. Oncogene, 2017, 36, 5551-5566.
[38]
Merlo, A.; Herman, J.G.; Mao, L.; Lee, D.J.; Gabrielson, E.; Burger, P.C.; Baylin, S.B.; Sidransky, D. 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat. Med., 1995, 1, 686-692.
[39]
Cameron, E.E.; Bachman, K.E.; Myohanen, S.; Herman, J.G.; Baylin, S.B. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet., 1999, 21, 103-107.
[40]
Shin, J.Y.; Kim, H.S.; Park, J.; Park, J.B.; Lee, J.Y. Mechanism for inactivation of the KIP family cyclin-dependent kinase inhibitor genes in gastric cancer cells. Cancer Res., 2000, 60, 262-265.
[41]
Dobrovic, A.; Simpfendorfer, D. Methylation of the BRCA1 gene in sporadic breast cancer. Cancer Res., 1997, 57, 3347-3350.
[42]
Catteau, A.; Harris, W.H.; Xu, C-F.; Solomon, E. Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: Correlation with disease characteristics. Oncogene, 1999, 18, 1957-1965.
[43]
Hua, K.T.; Wang, M.Y.; Chen, M.W.; Wei, L.H.; Chen, C.K.; Ko, C.H.; Jeng, Y.M.; Sung, P.L.; Jan, Y.H.; Hsiao, M.; Kuo, M.L.; Yen, M.L. The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis. Mol. Cancer, 2014, 13, 189-201.
[44]
Chen, M.W.; Hua, K.T.; Kao, H.J.; Chi, C.C.; Wei, L.H.; Johansson, G.; Shiah, S.G.; Chen, P.S.; Jeng, Y.M.; Cheng, T.Y.; Lai, T.C.; Chang, J.S.; Jan, Y.H.; Chien, M.H.; Yang, C.J.; Huang, M.S.; Hsiao, M.; Kuo, M.L. H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res., 2010, 70, 7830-7840.
[45]
Zhong, X.; Chen, X.; Guan, X.; Zhang, H.; Ma, Y.; Zhang, S.; Wang, E.; Zhang, L.; Han, Y. Overexpression of G9a and MCM7 in oesophageal squamous cell carcinoma is associated with poor prognosis. Histopathology, 2015, 66, 192-200.
[46]
Zhang, J.; He, P.; Xi, Y.; Geng, M.; Chen, Y.; Ding, J. Down-regulation of G9a triggers DNA damage response and inhibits colorectal cancer cells proliferation. Oncotarget, 2015, 6, 2917-2927.
[47]
Jones, P.A.; Taylor, S.M. Cellular differentiation, cytidine analogs and DNA methylation. Cell, 1980, 20, 85-93.
[48]
Rius, M.; Stresemann, C.; Keller, D.; Brom, M.; Schirrmacher, E.; Keppler, D.; Lyko, F. Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylation. Mol. Cancer Ther., 2009, 8, 225-231.
[49]
Ghoshal, K.; Datta, J.; Majumder, S.; Bai, S.; Kutay, H.; Motiwala, T.; Jacob, S.T. 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., 2005, 25, 4727-4741.
[50]
Stresemann, C.; Lyko, F. Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int. J. Cancer, 2008, 123, 8-13.
[51]
Hess, J.; Homann, S.; Laureano, N.K.; Tawk, B.; Bieg, M.; Hostenech, X.P.; Freier, K.; Weichert, W.; Zaoui, K. Tumor cell plasticity in the pathogenesis and prognosis of head and neck cancer. Laryngorhinootologie, 2018, 97, S94-S95.
[52]
Griffiths, E.; Choy, G.; Redkar, S.; Taverna, P.; Azab, M.; Karpf, A.R. Sgi-110: DNA methyltransferase inhibitor oncolytic. Drugs Future, 2013, 38, 535-543.
[53]
Issa, J-P.J.; Roboz, G.; Rizzieri, D.; Jabbour, E.; Stock, W.; O’Connell, C.; Yee, K.; Tibes, R.; Griffiths, E.A.; Walsh, K. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: A multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol., 2015, 16, 1099-1110.
[54]
San José-Enériz, E.; Agirre, X.; Rabal, O.; Vilas-Zornoza, A.; Sanchez-Arias, J.A.; Miranda, E.; Ugarte, A.; Roa, S.; Paiva, B.; de Mendoza, A.E-H. Discovery of first-in-class reversible dual small molecule inhibitors against G9a andDNMTs in hematological malignancies. Nat. Commun., 2017, 8, 15424.
[55]
Singh, N.; Dueñas‐González, A.; Lyko, F.; Medina‐Franco, J.L. Molecular modeling and molecular dynamics studies of hydralazine with human DNA methyltransferase 1. ChemMedChem, 2009, 4, 792-799.
[56]
Chuang, J.C.; Yoo, C.B.; Kwan, J.M.; Li, T.W.; Liang, G.; Yang, A.S.; Jones, P.A. Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2′-deoxycytidine. Mol. Cancer Ther., 2005, 4, 1515-1520.
[57]
Bedford, M.T.; Van Helden, P.D. Hypomethylation of DNA in pathological conditions of the human prostate. Cancer Res., 1987, 47, 5274-5276.
[58]
Wahlfors, J.; Hiltunen, H.; Heinonen, K.; Hamalainen, E.; Alhonen, L.; Janne, J. Genomic hypomethylation in human chronic lymphocytic leukemia. Blood, 1992, 80, 2074-2080.
[59]
Lin, C-H.; Hsieh, S-Y.; Sheen, I-S.; Lee, W-C.; Chen, T-C.; Shyu, W-C.; Liaw, Y-F. Genome-wide hypomethylation in hepatocellular carcinogenesis. Cancer Res., 2001, 61, 4238-4243.
[60]
Kim, Y.I.; Giuliano, A.; Hatch, K.D.; Schneider, A.; Nour, M.A.; Dallal, G.E.; Selhub, J.; Mason, J.B. Global DNA hypomethylation increases progressively in cervical dysplasia and carcinoma. Cancer, 1994, 74, 893-899.
[61]
Veland, N.; Hardikar, S.; Zhong, Y.; Gayatri, S.; Dan, J.; Strahl, B.D.; Rothbart, S.B.; Bedford, M.T.; Chen, T. The arginine methyltransferase PRMT6 regulates DNA methylation and contributes to global DNA hypomethylation in cancer. Cell Rep., 2017, 21, 3390-3397.
[62]
Perez, R.F.; Tejedor, J.R.; Bayon, G.F.; Fernández, A.F.; Fraga, M.F. Distinct chromatin signatures of DNA hypomethylation in aging and cancer. Aging Cell, 2018, 17e12744
[63]
Berger, S.L. The complex language of chromatin regulation during transcription. Nature, 2007, 447, 407-412.
[64]
Buschbeck, M.; Hake, S.B. Variants of core histones and their roles in cell fate decisions, development and cancer. Nat. Rev. Mol. Cell Biol., 2017, 18, 299-314.
[65]
Biswas, S.; Rao, C.M. Epigenetics in cancer: Fundamentals and beyond. Pharmacol. Ther., 2017, 173, 118-134.
[66]
Taverna, S.D.; Li, H.; Ruthenburg, A.J.; Allis, C.D.; Patel, D.J. How chromatin-binding modules interpret histone modifications: Lessons from professional pocket pickers. Nat. Struct. Mol. Biol., 2007, 14, 1025-1040.
[67]
Falkenberg, K.J.; Johnstone, R.W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat. Rev. Drug Discov., 2014, 13, 673-691.
[68]
Perego, P.; Zuco, V.; Gatti, L.; Zunino, F. Sensitization of tumor cells by targeting histone deacetylases. Biochem. Pharmacol., 2012, 83, 987-994.
[69]
Wang, L.; Li, H.; Ren, Y.; Zou, S.; Fang, W.; Jiang, X.; Jia, L.; Li, M.; Liu, X.; Yuan, X. Targeting HDAC with a novel inhibitor effectively reverses paclitaxel resistance in non-small cell lung cancer via multiple mechanisms. Cell Death Dis., 2017, 7e2063
[70]
Wei, Y.; Zhou, F.; Lin, Z.; Shi, L.; Huang, A.; Liu, T.; Yu, D.; Wu, G. Antitumor effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid in epidermal growth factor receptor-mutant non-small-cell lung cancer lines in vitro and in vivo. Anticancer Drugs, 2018, 29, 262-270.
[71]
Ye, C.; Han, K.; Lei, J.; Zeng, K.; Zeng, S.; Ju, H.; Yu, L. Inhibition of HDAC7 reverses CNT2 repression in colorectal cancer by up‐regulating histone acetylation state. Br. J. Pharmacol., 2018, 175(22), 4209-4217.
[72]
Ansari, J.; Shackelford, R.E.; El-Osta, H. Epigenetics in non-small cell lung cancer: From basics to therapeutics. Transl. Lung Cancer Res., 2016, 5, 155-171.
[73]
Mukhopadhyay, N.K.; Weisberg, E.; Gilchrist, D.; Bueno, R.; Sugarbaker, D.J.; Jaklitsch, M.T. Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non–small-cell lung cancer. Ann. Thorac. Surg., 2006, 81, 1034-1042.
[74]
Gottlicher, M.; Minucci, S.; Zhu, P.; Kramer, O.H.; Schimpf, A.; Giavara, S.; Sleeman, J.P.; Lo Coco, F.; Nervi, C.; Pelicci, P.G.; Heinzel, T. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J., 2001, 20, 6969-6978.
[75]
Gavrilov, V.; Lavrenkov, K.; Ariad, S.; Shany, S. Sodium valproate, a histone deacetylase inhibitor, enhances the efficacy of vinorelbine-cisplatin-based chemoradiation in non-small cell lung cancer cells. Anticancer Res., 2014, 34, 6565-6572.
[76]
Shirsath, N.; Rathos, M.; Chaudhari, U.; Sivaramakrishnan, H.; Joshi, K. Potentiation of anticancer effect of valproic acid, an antiepileptic agent with histone deacetylase inhibitory activity, by the cyclin-dependent kinase inhibitor P276-00 in human non-small-cell lung cancer cell lines. Lung Cancer, 2013, 82, 214-221.
[77]
Greve, G.; Schiffmann, I.; Pfeifer, D.; Pantic, M.; Schüler, J.; Lübbert, M. The pan-HDAC inhibitor panobinostat acts as a sensitizer for erlotinib activity in EGFR-mutated and-wildtype non-small cell lung cancer cells. BMC Cancer, 2015, 15, 947-956.
[78]
Filippakopoulos, P.; Qi, J.; Picaud, S.; Shen, Y.; Smith, W.B.; Fedorov, O.; Morse, E.M.; Keates, T.; Hickman, T.T.; Felletar, I. Selective inhibition of BET bromodomains. Nature, 2010, 468, 1067-1073.
[79]
Sakaguchi, T.; Yoshino, H.; Sugita, S.; Osako, Y.; Yonemori, M.; Miyamoto, K.; Nakagawa, M.; Enokida, H. Bromodomain protein BRD4 inhibition as a novel therapeutic approach in sunitinib-resistant renal cell carcinoma. Eur. Urol. Suppl., 2018, 17e60
[80]
Pérez-Salvia, M.; Esteller, M. Bromodomain inhibitors and cancer therapy: From structures to applications. Epigenetics, 2017, 12, 323-339.
[81]
Zhang, Y.; Reinberg, D. Transcription regulation by histone methylation: Interplay between different covalent modifications of the core histone tails. Genes Dev., 2001, 15, 2343-2360.
[82]
Viré, E.; Brenner, C.; Deplus, R.; Blanchon, L.; Fraga, M.; Didelot, C.; Morey, L.; Van Eynde, A.; Bernard, D.; Vanderwinden, J-M. The polycomb group protein EZH2 directly controls DNA methylation. Nature, 2006, 439, 871-874.
[83]
Song, Y.; Wu, F.; Wu, J. Targeting histone methylation for cancer therapy: Enzymes, inhibitors, biological activity and perspectives. J. Hematol. Oncol., 2016, 9, 49.
[84]
Kim, W.; Kim, R.; Park, G.; Park, J-W.; Kim, J-E. Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation. J. Biol. Chem., 2012, 287, 5588-5599.
[85]
Daigle, S.R.; Olhava, E.J.; Therkelsen, C.A.; Majer, C.R.; Sneeringer, C.J.; Song, J.; Johnston, L.D.; Scott, M.P.; Smith, J.J.; Xiao, Y. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell, 2011, 20, 53-65.
[86]
Blanc, R.S.; Richard, S. Arginine methylation: The coming of age. Mol. Cell, 2017, 65, 8-24.
[87]
Chan-Penebre, E.; Kuplast, K.G.; Majer, C.R.; Boriack-Sjodin, P.A.; Wigle, T.J.; Johnston, L.D.; Rioux, N.; Munchhof, M.J.; Jin, L.; Jacques, S.L. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat. Chem. Biol., 2015, 11, 432-437.
[88]
Avasarala, S.; Van Scoyk, M.; Rathinam, M.K.K.; Zerayesus, S.; Zhao, X.; Zhang, W.; Pergande, M.R.; Borgia, J.A.; DeGregori, J.; Port, J.D. PRMT1 is a novel regulator of epithelial-mesenchymal-transition in non-small cell lung cancer. J. Biol. Chem., 2015, 290, 13479-13489.
[89]
Yao, R.; Jiang, H.; Ma, Y.; Wang, L.; Wang, L.; Du, J.; Hou, P.; Gao, Y.; Zhao, L.; Wang, G. PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer. Cancer Res., 2014, 74, 5656-5667.
[90]
Rossetto, D.; Avvakumov, N.; Côté, J. Histone phosphorylation: A chromatin modification involved in diverse nuclear events. Epigenetics, 2012, 7, 1098-1108.
[91]
Li, B.; Huang, G.; Zhang, X.; Li, R.; Wang, J.; Dong, Z.; He, Z. Increased phosphorylation of histone H3 at serine 10 is involved in Epstein-Barr virus latent membrane protein-1-induced carcinogenesis of nasopharyngeal carcinoma. BMC Cancer, 2013, 13, 124.
[92]
Kouzarides, T. Chromatin modifications and their function. Cell, 2007, 128, 693-705.
[93]
Fischle, W.; Tseng, B.S.; Dormann, H.L.; Ueberheide, B.M.; Garcia, B.A.; Shabanowitz, J.; Hunt, D.F.; Funabiki, H.; Allis, C.D. Regulation of HP1–chromatin binding by histone H3 methylation and phosphorylation. Nature, 2005, 438, 1116-1122.
[94]
Li, M.; Dong, Q.; Zhu, B. Aurora Kinase B phosphorylates histone H3.3 at serine 31 during mitosis in mammalian cells. J. Mol. Biol., 2017, 429, 2042-2045.
[95]
Aihara, H.; Nakagawa, T.; Yasui, K.; Ohta, T.; Hirose, S.; Dhomae, N.; Takio, K.; Kaneko, M.; Takeshima, Y.; Muramatsu, M. Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo. Genes Dev., 2004, 18, 877-888.
[96]
Sawicka, A.; Seiser, C. Sensing core histone phosphorylation-a matter of perfect timing. Biochim. Biophys. Acta. Gene Regul. Mech., 2014, 1839, 711-718.
[97]
Pickart, C.M. Mechanisms underlying ubiquitination. Annu. Rev. Biochem., 2001, 70, 503-533.
[98]
Goldknopf, I.; Taylor, C.W.; Baum, R.M.; Yeoman, L.C.; Olson, M.; Prestayko, A.; Busch, H. Isolation and characterization of protein A24, a "histone-like" non-histone chromosomal protein. J. Biol. Chem., 1975, 250, 7182-7187.
[99]
Osley, M.A. Regulation of histone H2A and H2B ubiquitylation. Brief. Funct. Genomics, 2006, 5, 179-189.
[100]
McClurg, U.L.; Robson, C.N. Deubiquitinating enzymes as oncotargets. Oncotarget, 2015, 6, 9657-9668.
[101]
Davie, J.R.; Murphy, L.C. Inhibition of transcription selectively reduces the level of ubiquitinated histone H2B in chromatin. Biochem. Biophys. Res. Commun., 1994, 203, 344-350.
[102]
Dwane, L.; Gallagher, W.M.; Chonghaile, T.N.; O’Connor, D.P. The emerging role of non-traditional ubiquitination in oncogenic pathways. J. Biol. Chem., 2017, 292, 3543-3551.
[103]
Melchior, F. SUMO-nonclassical ubiquitin. Annu. Rev. Cell Dev. Biol., 2000, 16, 591-626.
[104]
Gostissa, M.; Hengstermann, A.; Fogal, V.; Sandy, P.; Schwarz, S.E.; Scheffner, M.; Del Sal, G. Activation of p53 by conjugation to the ubiquitin‐like protein SUMO‐1. EMBO J., 1999, 18, 6462-6471.
[105]
Buschmann, T.; Fuchs, S.Y.; Lee, C-G.; Pan, Z-Q.; Ronai, Z. SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell, 2000, 101, 753-762.
[106]
Müller, S.; Matunis, M.J.; Dejean, A. Conjugation with the ubiquitin‐related modifier SUMO‐1 regulates the partitioning of PML within the nucleus. EMBO J., 1998, 17, 61-70.
[107]
Shiio, Y.; Eisenman, R.N. Histone sumoylation is associated with transcriptional repression. Proc. Natl. Acad. Sci. USA, 2003, 100, 13225-13230.
[108]
Dhall, A.; Weller, C.E.; Chu, A.; Shelton, P.M.; Chatterjee, C. Chemically sumoylated histone H4 stimulates intranucleosomal demethylation by the LSD1-CoREST complex. ACS Chem. Biol., 2017, 12, 2275-2280.
[109]
Shanmugam, M.K.; Arfuso, F.; Arumugam, S.; Chinnathambi, A.; Jinsong, B.; Warrier, S.; Wang, L.Z.; Kumar, A.P.; Ahn, K.S.; Sethi, G. Role of novel histone modifications in cancer. Oncotarget, 2018, 9, 11414-11426.
[110]
Fukuto, A.; Ikura, M.; Ikura, T.; Sun, J.; Horikoshi, Y.; Shima, H.; Igarashi, K.; Kusakabe, M.; Harata, M.; Horikoshi, N. SUMO modification system facilitates the exchange of histone variant H2A. Z-2 at DNA damage sites. Nucleus, 2018, 9, 87-94.
[111]
Han, Z-J.; Feng, Y-H.; Gu, B-H.; Li, Y-M.; Chen, H. The post-translational modification, sumoylation, and cancer. Int. J. Oncol., 2018, 52, 1081-1094.
[112]
Kamitani, T.; Kito, K.; Nguyen, H.P.; Yeh, E.T. Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein. J. Biol. Chem., 1997, 272, 28557-28562.
[113]
Duda, D.M.; Borg, L.A.; Scott, D.C.; Hunt, H.W.; Hammel, M.; Schulman, B.A. Structural insights into NEDD8 activation of cullin-RING ligases: Conformational control of conjugation. Cell, 2008, 134, 995-1006.
[114]
Salon, C.; Brambilla, E.; Brambilla, C.; Lantuejoul, S.; Gazzeri, S.; Eymin, B. Altered pattern of Cul‐1 protein expression and neddylation in human lung tumours: Relationships with CAND1 and cyclin E protein levels. J. Pathol., 2007, 213, 303-310.
[115]
Zhou, L.; Zhang, W.; Sun, Y.; Jia, L. Protein neddylation and its alterations in human cancers for targeted therapy. Cell. Signal., 2018, •••, 92-102.
[116]
Li, L.; Wang, M.; Yu, G.; Chen, P.; Li, H.; Wei, D.; Zhu, J.; Xie, L.; Jia, H.; Shi, J. Overactivated neddylation pathway as a therapeutic target in lung cancer. J. Natl. Cancer Inst., 2014, 106dju083
[117]
Li, T.; Guan, J.; Huang, Z.; Hu, X.; Zheng, X. RNF168-mediated H2A neddylation antagonizes ubiquitylation of H2A and regulates DNA damage repair. J. Cell Sci., 2014, 127, 2238-2248.
[118]
Ma, T.; Chen, Y.; Zhang, F.; Yang, C-Y.; Wang, S.; Yu, X. RNF111-dependent neddylation activates DNA damage-induced ubiquitination. Mol. Cell, 2013, 49, 897-907.
[119]
Soucy, T.A.; Smith, P.G.; Milhollen, M.A.; Berger, A.J.; Gavin, J.M.; Adhikari, S.; Brownell, J.E.; Burke, K.E.; Cardin, D.P.; Critchley, S. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature, 2009, 458, 732-736.
[120]
Swords, R.T.; Savona, M.R.; Maris, M.B.; Erba, H.P.; Berdeja, J.G.; Foran, J.M.; Hua, Z.; Faessel, H.M.; Dash, A.B.; Sedarati, F. Pevonedistat (MLN4924), an investigational, first-in-class NAE inhibitor, in combination with azacitidine in elderly patients with acute myeloid leukemia (AML) considered unfit for conventional chemotherapy: Updated results from the phase 1 C15009 trial. Blood, 2014, 124, 2313.
[121]
Liu, N.; Pan, T. RNA epigenetics. Translational Res., 2015, 165, 28-35.
[122]
Song, X.; Nazar, R.N. Modification of rRNA as a ‘quality control mechanism’in ribosome biogenesis. FEBS Lett., 2002, 523, 182-186.
[123]
Agris, P.F. Decoding the genome: A modified view. Nucleic Acids Res., 2004, 32, 223-238.
[124]
Wei, C-M.; Gershowitz, A.; Moss, B. N6, O2′-dimethyladenosine a novel methylated ribonucleoside next to the 5′ terminal of animal cell and virus mRNAs. Nature, 1975, 257, 251-253.
[125]
Narayan, P.; Rottman, F.M. An in vitro system for accurate methylation of internal adenosine residues in messenger RNA. Science, 1988, 242, 1159-1162.
[126]
Squires, J.E.; Patel, H.R.; Nousch, M.; Sibbritt, T.; Humphreys, D.T.; Parker, B.J.; Suter, C.M.; Preiss, T. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res., 2012, 40, 5023-5033.
[127]
Bokar, J.A. The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA. In Fine-tuning of RNA functions by modification and editing; Springer, 2005, pp. 141-177.
[128]
Lin, S.; Choe, J.; Du, P.; Triboulet, R.; Gregory, R.I. The m 6 A methyltransferase METTL3 promotes translation in human cancer cells. Mol. Cell, 2016, 62, 335-345.
[129]
Batista, P.J.; Molinie, B.; Wang, J.; Qu, K.; Zhang, J.; Li, L.; Bouley, D.M.; Lujan, E.; Haddad, B.; Daneshvar, K. M6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell, 2014, 15, 707-719.
[130]
Geula, S.; Moshitch-Moshkovitz, S.; Dominissini, D.; Mansour, A.A.; Kol, N.; Salmon-Divon, M.; Hershkovitz, V.; Peer, E.; Mor, N.; Manor, Y.S. M6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science, 2015, 347, 1002-1006.
[131]
Xiang, Y.; Laurent, B.; Hsu, C-H.; Nachtergaele, S.; Lu, Z.; Sheng, W.; Xu, C.; Chen, H.; Ouyang, J.; Wang, S. RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature, 2017, 543, 573-576.
[132]
Calin, G.A.; Croce, C.M. MicroRNA signatures in human cancers. Nat. Rev. Cancer, 2006, 6, 857-866.
[133]
Friedman, R.C.; Farh, K.K-H.; Burge, C.B.; Bartel, D.P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res., 2009, 19, 92-105.
[134]
Lopez-Serra, P.; Esteller, M. DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene, 2012, 31, 1609-1622.
[135]
Guil, S.; Esteller, M. DNA methylomes, histone codes and miRNAs: Tying it all together. Int. J. Biochem. Cell Biol., 2009, 41, 87-95.
[136]
Anastasiadou, E.; Jacob, L.S.; Slack, F.J. Non-coding RNA networks in cancer. Nat. Rev. Cancer, 2018, 18, 5-18.
[137]
Schmitt, A.M.; Chang, H.Y. Long noncoding RNAs in cancer pathways. Cancer Cell, 2016, 29, 452-463.
[138]
Chu, C.; Zhang, Q.C.; Da Rocha, S.T.; Flynn, R.A.; Bharadwaj, M.; Calabrese, J.M.; Magnuson, T.; Heard, E.; Chang, H.Y. Systematic discovery of Xist RNA binding proteins. Cell, 2015, 161, 404-416.
[139]
Gupta, R.A.; Shah, N.; Wang, K.C.; Kim, J.; Horlings, H.M.; Wong, D.J.; Tsai, M-C.; Hung, T.; Argani, P.; Rinn, J.L. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 2010, 464, 1071-1076.
[140]
Morlando, M.; Fatica, A. Alteration of epigenetic regulation by long noncoding RNAs in cancer. Int. J. Mol. Sci., 2018, 19E570
[141]
Kurdyukov, S.; Bullock, M. DNA methylation analysis: Choosing the right method. Biology, 2016, 5, 3-24.
[142]
Smith, E.; Jones, M.E.; Drew, P.A. Quantitation of DNA methylation by melt curve analysis. BMC Cancer, 2009, 9, 123.
[143]
Mundade, R.; Ozer, H.G.; Wei, H.; Prabhu, L.; Lu, T. Role of ChIP-seq in the discovery of transcription factor binding sites, differential gene regulation mechanism, epigenetic marks and beyond. Cell Cycle, 2014, 13, 2847-2852.
[144]
Natarajan, A.; Yardımcı, G.G.; Sheffield, N.C.; Crawford, G.E.; Ohler, U. Predicting cell-type–specific gene expression from regions of open chromatin. Genome Res., 2012, 22, 1711-1722.
[145]
Tripathi, R.; Chakraborty, P.; Varadwaj, P.K. Unraveling long non-coding RNAs through analysis of high-throughput RNA-sequencing data. Noncoding RNA Res., 2017, 2, 111-118.
[146]
Peleg, S.; Sananbenesi, F.; Zovoilis, A.; Burkhardt, S.; Bahari-Javan, S.; Agis-Balboa, R.C.; Cota, P.; Wittnam, J.L.; Gogol-Doering, A.; Opitz, L. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science, 2010, 328, 753-756.
[147]
Lin, H.S.; Hu, C.Y.; Chan, H.Y.; Liew, Y.Y.; Huang, H.P.; Lepescheux, L.; Bastianelli, E.; Baron, R.; Rawadi, G.; Clément‐Lacroix, P. Anti‐rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen‐induced arthritis in rodents. Br. J. Pharmacol., 2007, 150, 862-872.
[148]
Hockly, E.; Richon, V.M.; Woodman, B.; Smith, D.L.; Zhou, X.; Rosa, E.; Sathasivam, K.; Ghazi-Noori, S.; Mahal, A.; Lowden, P.A. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc. Natl. Acad. Sci. USA, 2003, 100, 2041-2046.
[149]
Alarcón, J.M.; Malleret, G.; Touzani, K.; Vronskaya, S.; Ishii, S.; Kandel, E.R.; Barco, A. Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: A model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron, 2004, 42, 947-959.
[150]
Brogdon, J.L.; Xu, Y.; Szabo, S.J.; An, S.; Buxton, F.; Cohen, D.; Huang, Q. Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function. Blood, 2007, 109, 1123-1130.
[151]
Adcock, I. Hdac inhibitors as anti‐inflammatory agents. Br. J. Pharmacol., 2007, 150, 829-831.
[152]
Qing, H.; He, G.; Ly, P.T.; Fox, C.J.; Staufenbiel, M.; Cai, F.; Zhang, Z.; Wei, S.; Sun, X.; Chen, C-H. Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer’s disease mouse models. J. Exp. Med., 2008, 205, 2781-2789.
[153]
Tao, R.; De Zoeten, E.F.; Özkaynak, E.; Chen, C.; Wang, L.; Porrett, P.M.; Li, B.; Turka, L.A.; Olson, E.N.; Greene, M.I. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat. Med., 2007, 13, 1299-1307.
[154]
McGee, S.L.; Hargreaves, M. Exercise and skeletal muscle glucose transporter 4 expression: Molecular mechanisms. Clin. Exp. Pharmacol. Physiol., 2006, 33, 395-399.
[155]
Daneshpajooh, M.; Bacos, K.; Bysani, M.; Bagge, A.; Laakso, E.O.; Vikman, P.; Eliasson, L.; Mulder, H.; Ling, C. HDAC7 is overexpressed in human diabetic islets and impairs insulin secretion in rat islets and clonal beta cells. Diabetologia, 2017, 60, 116-125.
[156]
Xu, Z.; Tong, Q.; Zhang, Z.; Wang, S.; Zheng, Y.; Liu, Q.; Qian, L.; Chen, S-y.; Sun, J.; Cai, L. Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway. Clin. Sci., 2017, 131, 1841-1857.
[157]
Dong, E.; Grayson, D.R.; Guidotti, A.; Ruzicka, W.; Veldic, M.; Costa, E. Reviewing the role of DNA (cytosine-5) methyltransferase overexpression in the cortical GABAergic dysfunction associated with psychosis vulnerability. Epigenetics, 2007, 2, 29-36.
[158]
Matt, S.M.; Zimmerman, J.D.; Lawson, M.A.; Bustamante, A.C.; Uddin, M.; Johnson, R.W. Inhibition of DNA methylation with zebularine alters lipopolysaccharide-induced sickness behavior and neuroinflammation in mice. Front. Neurosci., 2018, 12, 636.
[159]
Fonteneau, M.; Filliol, D.; Anglard, P.; Befort, K.; Romieu, P.; Zwiller, J. Inhibition of DNA methyltransferases regulates cocaine self‐administration by rats: A genome‐wide DNA methylation study. Genes Brain Behav., 2017, 16, 313-327.
[160]
Hedrich, C.M.; Mäbert, K.; Rauen, T.; Tsokos, G.C. DNA methylation in systemic lupus erythematosus. Epigenomics, 2017, 9, 505-525.
[161]
Sato, T.; Issa, J.; Kropf, P.; Hypomethylating Drugs, D.N.A. Drugs in Cancer Therapy. Cold Spring Harb. Perspect. Med., 2017, 7a026948
[162]
Castro, K.; Casaccia, P. Epigenetic modifications in brain and immune cells of multiple sclerosis patients. Mult. Scler. J., 2018, 24, 69-74.
[163]
Zhao, Y. Garcia, B.A. Comprehensive Catalog of Currently Documented Histone Modifications. Cold Spring Harb. Perspect. Biol., 2015, 7a025064
[164]
Dawson, M.A. Bannister; A.J.; Göttgens B.; Foster, S.D.; Bartke, T.; Green, A.R.; Kouzarides, T. JAK2 phosphorylates histone H3Y41 and excludes HP1α from chromatin. Nature, 2009, 461, 819-822.
[165]
Chou, R.H. Wang, Y.N.; Hsieh, Y.H.; Li, L.Y.; Xia, W.; Chang, W.C.; Chang, L.C.; Cheng, C. C.; Lai, C.C.; Hsu, J.L.; Chang, W.J.; Chiang, S.Y.; Lee, H. J.; Liao, H. W.; Chuang, P. H.; Chen, H.Y.; Wang, H.L.; Kuo, S.C.; Chen, C.H.; Yu, Y.L.; Hung, M.C. EGFR modulates DNA synthesis and repair through Tyr phosphorylation of histone H4. Dev. Cell, 2014, 30, 224-237.

© 2024 Bentham Science Publishers | Privacy Policy