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Epigenetic Regulation in Cystogenesis

  • Yu Mi WooEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 933)

Abstract

Epigenetic regulation refers to heritable changes in gene expression that do not involve any alteration of the DNA sequence. DNA methylation, histone modification, and gene regulation by microRNAs are well-known epigenetic modulations that are closely associated with several cellular processes and diverse disease states, such as cancers, even under precancerous conditions. More recently, several studies have indicated that epigenetic changes may be associated with renal cystic diseases, including autosomal dominant polycystic kidney disease, and the restoration of altered epigenetic factors may become a therapeutic target of renal cystic disease and would be expected to have minimal side effects. This review focuses on recently reported findings on epigenetic and considers the potential of targeting epigenetic regulation as a novel therapeutic approach to control cystogenesis.

Keywords

Epigenetic regulation Cyst PKD 

References

  1. Aran D, Toperoff G, Rosenberg M, Hellman A (2011) Replication timing-related and gene body-specific methylation of active human genes. Hum Mol Genet 20(4):670–680. doi: 10.1093/hmg/ddq513 CrossRefPubMedGoogle Scholar
  2. Ben-Dov IZ, Tan YC, Morozov P, Wilson PD, Rennert H, Blumenfeld JD, Tuschl T (2014) Urine microRNA as potential biomarkers of autosomal dominant polycystic kidney disease progression: description of miRNA profiles at baseline. PLoS One 9(1):e86856. doi: 10.1371/journal.pone.0086856 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9(16):2395–2402CrossRefPubMedGoogle Scholar
  4. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16(1):6–21. doi: 10.1101/gad.947102 CrossRefPubMedGoogle Scholar
  5. Cao Y, Semanchik N, Lee SH, Somlo S, Barbano PE, Coifman R, Sun Z (2009) Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models. Proc Natl Acad Sci U S A 106(51):21819–21824. doi: 10.1073/pnas.0911987106 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomaki P, Lang JC, Schuller DE, Yu L, Bloomfield CD, Caligiuri MA, Yates A, Nishikawa R, Su Huang H, Petrelli NJ, Zhang X, O’Dorisio MS, Held WA, Cavenee WK, Plass C (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 24(2):132–138. doi: 10.1038/72785 CrossRefPubMedGoogle Scholar
  7. Deaton AM, Webb S, Kerr AR, Illingworth RS, Guy J, Andrews R, Bird A (2011) Cell type-specific DNA methylation at intragenic CpG islands in the immune system. Genome Res 21(7):1074–1086. doi: 10.1101/gr.118703.110 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Deribe YL, Wild P, Chandrashaker A, Curak J, Schmidt MH, Kalaidzidis Y, Milutinovic N, Kratchmarova I, Buerkle L, Fetchko MJ, Schmidt P, Kittanakom S, Brown KR, Jurisica I, Blagoev B, Zerial M, Stagljar I, Dikic I (2009) Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Sci Signal 2(102):ra84. doi: 10.1126/scisignal.2000576 PubMedGoogle Scholar
  9. Dweep H, Sticht C, Kharkar A, Pandey P, Gretz N (2013) Parallel analysis of mRNA and microRNA microarray profiles to explore functional regulatory patterns in polycystic kidney disease: using PKD/Mhm rat model. PLoS One 8(1):e53780. doi: 10.1371/journal.pone.0053780 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Esau CC, Monia BP (2007) Therapeutic potential for microRNAs. Adv Drug Deliv Rev 59(2-3):101–114. doi: 10.1016/j.addr.2007.03.007 CrossRefPubMedGoogle Scholar
  11. Esteller M (2005) Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol 45:629–656. doi: 10.1146/annurev.pharmtox.45.120403.095832 CrossRefPubMedGoogle Scholar
  12. Fan LX, Li X, Magenheimer B, Calvet JP (2012) Inhibition of histone deacetylases targets the transcription regulator Id2 to attenuate cystic epithelial cell proliferation. Kidney Int 81(1):76–85. doi: 10.1038/ki.2011.296 CrossRefPubMedGoogle Scholar
  13. Felsenfeld G, Groudine M (2003) Controlling the double helix. Nature 421(6921):448–453. doi: 10.1038/nature01411 CrossRefPubMedGoogle Scholar
  14. Gius D, Cui H, Bradbury CM, Cook J, Smart DK, Zhao S, Young L, Brandenburg SA, Hu Y, Bisht KS, Ho AS, Mattson D, Sun L, Munson PJ, Chuang EY, Mitchell JB, Feinberg AP (2004) Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach. Cancer Cell 6(4):361–371. doi: 10.1016/j.ccr.2004.08.029 CrossRefPubMedGoogle Scholar
  15. Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP (2007) MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27(1):91–105. doi: 10.1016/j.molcel.2007.06.017 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Gupta S, Kim SY, Artis S, Molfese DL, Schumacher A, Sweatt JD, Paylor RE, Lubin FD (2010) Histone methylation regulates memory formation. J Neurosci Off J Soc Neurosci 30(10):3589–3599. doi: 10.1523/JNEUROSCI.3732-09.2010 CrossRefGoogle Scholar
  17. Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349(21):2042–2054. doi: 10.1056/NEJMra023075 CrossRefPubMedGoogle Scholar
  18. Hu HY, Yan Z, Xu Y, Hu H, Menzel C, Zhou YH, Chen W, Khaitovich P (2009) Sequence features associated with microRNA strand selection in humans and flies. BMC Genomics 10:413. doi: 10.1186/1471-2164-10-413 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Illingworth R, Kerr A, Desousa D, Jorgensen H, Ellis P, Stalker J, Jackson D, Clee C, Plumb R, Rogers J, Humphray S, Cox T, Langford C, Bird A (2008) A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol 6(1):e22. doi: 10.1371/journal.pbio.0060022 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Juttermann R, Li E, Jaenisch R (1994) Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci U S A 91(25):11797–11801CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10(2):126–139. doi: 10.1038/nrm2632 CrossRefPubMedGoogle Scholar
  22. Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705. doi: 10.1016/j.cell.2007.02.005 CrossRefPubMedGoogle Scholar
  23. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438(7068):685–689. doi: 10.1038/nature04303 CrossRefPubMedGoogle Scholar
  24. Laird PW, Jackson-Grusby L, Fazeli A, Dickinson SL, Jung WE, Li E, Weinberg RA, Jaenisch R (1995) Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81(2):197–205CrossRefPubMedGoogle Scholar
  25. Lakhia R, Hajarnis S, Williams D, Aboudehen K, Yheskel M, Xing C, Hatley ME, Torres VE, Wallace DP, Patel V (2015) MicroRNA-21 aggravates cyst growth in a model of polycystic kidney disease. J Am Soc Nephrol JASN. doi: 10.1681/ASN.2015060634 PubMedGoogle Scholar
  26. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854CrossRefPubMedGoogle Scholar
  27. Lee SO, Masyuk T, Splinter P, Banales JM, Masyuk A, Stroope A, Larusso N (2008) MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Invest 118(11):3714–3724. doi: 10.1172/JCI34922 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Li X (2011) Epigenetics and autosomal dominant polycystic kidney disease. Biochim Biophys Acta 1812(10):1213–1218. doi: 10.1016/j.bbadis.2010.10.008 CrossRefPubMedGoogle Scholar
  29. Lindow M, Gorodkin J (2007) Principles and limitations of computational microRNA gene and target finding. DNA Cell Biol 26(5):339–351. doi: 10.1089/dna.2006.0551 CrossRefPubMedGoogle Scholar
  30. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315–322. doi: 10.1038/nature08514 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Liu W, Fan LX, Zhou X, Sweeney WE Jr, Avner ED, Li X (2012) HDAC6 regulates epidermal growth factor receptor (EGFR) endocytic trafficking and degradation in renal epithelial cells. PLoS One 7(11):e49418. doi: 10.1371/journal.pone.0049418 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105(30):10513–10518. doi: 10.1073/pnas.0804549105 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Nahhas F, Dryden SC, Abrams J, Tainsky MA (2007) Mutations in SIRT2 deacetylase which regulate enzymatic activity but not its interaction with HDAC6 and tubulin. Mol Cell Biochem 303(1-2):221–230. doi: 10.1007/s11010-007-9478-6 CrossRefPubMedGoogle Scholar
  34. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (2003) The human Sir2 ortholog, SIRT2, is an NAD + -dependent tubulin deacetylase. Mol Cell 11(2):437–444CrossRefPubMedGoogle Scholar
  35. Noureddine L, Hajarnis S, Patel V (2013) MicroRNAs and polycystic kidney disease. Drug Discov Today Dis Mod 10(3):e137–e1743. doi: 10.1016/j.ddmod.2013.10.001 CrossRefGoogle Scholar
  36. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247–257CrossRefPubMedGoogle Scholar
  37. Pandey P, Brors B, Srivastava PK, Bott A, Boehn SN, Groene HJ, Gretz N (2008) Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease. BMC Genomics 9:624. doi: 10.1186/1471-2164-9-624 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Pandey P, Qin S, Ho J, Zhou J, Kreidberg JA (2011) Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease. BMC Syst Biol 5:56. doi: 10.1186/1752-0509-5-56 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Pastorelli LM, Wells S, Fray M, Smith A, Hough T, Harfe BD, McManus MT, Smith L, Woolf AS, Cheeseman M, Greenfield A (2009) Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract. Mamm Genome Off J Int Mamm Genome Soc 20(3):140–151. doi: 10.1007/s00335-008-9169-y CrossRefGoogle Scholar
  40. Patel V, Noureddine L (2012) MicroRNAs and fibrosis. Curr Opin Nephrol Hypertens 21(4):410–416. doi: 10.1097/MNH.0b013e328354e559 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Patel V, Hajarnis S, Williams D, Hunter R, Huynh D, Igarashi P (2012) MicroRNAs regulate renal tubule maturation through modulation of Pkd1. J Am Soc Nephrol JASN 23(12):1941–1948. doi: 10.1681/ASN.2012030321 CrossRefPubMedGoogle Scholar
  42. Patel V, Williams D, Hajarnis S, Hunter R, Pontoglio M, Somlo S, Igarashi P (2013) miR-17 ~ 92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease. Proc Natl Acad Sci U S A 110(26):10765–10770. doi: 10.1073/pnas.1301693110 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Sawan C, Herceg Z (2010) Histone modifications and cancer. Adv Genet 70:57–85. doi: 10.1016/B978-0-12-380866-0.60003-4 PubMedGoogle Scholar
  44. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455(7209):58–63. doi: 10.1038/nature07228 CrossRefPubMedGoogle Scholar
  45. Taby R, Issa JP (2010) Cancer epigenetics. CA Cancer J Clin 60(6):376–392. doi: 10.3322/caac.20085 CrossRefPubMedGoogle Scholar
  46. Tran U, Zakin L, Schweickert A, Agrawal R, Doger R, Blum M, De Robertis EM, Wessely O (2010) The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development 137(7):1107–1116. doi: 10.1242/dev.046045 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Van Bodegom D, Saifudeen Z, Dipp S, Puri S, Magenheimer BS, Calvet JP, El-Dahr SS (2006) The polycystic kidney disease-1 gene is a target for p53-mediated transcriptional repression. J Biol Chem 281(42):31234–31244. doi: 10.1074/jbc.M606510200 CrossRefPubMedGoogle Scholar
  48. van Bodegom D, Roessingh W, Pridjian A, El Dahr SS (2010) Mechanisms of p53-mediated repression of the human polycystic kidney disease-1 promoter. Biochim Biophys Acta 1799(7):502–509. doi: 10.1016/j.bbagrm.2010.04.001 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K (2010) The microRNA spectrum in 12 body fluids. Clin Chem 56(11):1733–1741. doi: 10.1373/clinchem.2010.147405 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Woo YM, Bae JB, Oh YH, Lee YG, Lee MJ, Park EY, Choi JK, Lee S, Shin Y, Lyu J, Jung HY, Lee YS, Hwang YH, Kim YJ, Park JH (2014) Genome-wide methylation profiling of ADPKD identified epigenetically regulated genes associated with renal cyst development. Hum Genet 133(3):281–297. doi: 10.1007/s00439-013-1378-0 CrossRefPubMedGoogle Scholar
  51. Woo YM, Shin Y, Hwang JA, Hwang YH, Lee S, Park EY, Kong HK, Park HC, Lee YS, Park JH (2015) Epigenetic silencing of the MUPCDH gene as a possible prognostic biomarker for cyst growth in ADPKD. Sci Rep 5:15238. doi: 10.1038/srep15238 CrossRefPubMedGoogle Scholar
  52. Xia S, Li X, Johnson T, Seidel C, Wallace DP, Li R (2010) Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development 137(7):1075–1084. doi: 10.1242/dev.049437 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Yang JS, Lai EC (2011) Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Mol Cell 43(6):892–903. doi: 10.1016/j.molcel.2011.07.024 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Yoo CB, Jones PA (2006) Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 5(1):37–50. doi: 10.1038/nrd1930 CrossRefPubMedGoogle Scholar
  55. Zen K, Zhang CY (2012) Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev 32(2):326–348. doi: 10.1002/med.20215 CrossRefPubMedGoogle Scholar
  56. Zhang Y, Reinberg D (2001) Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev 15(18):2343–2360. doi: 10.1101/gad.927301 CrossRefPubMedGoogle Scholar
  57. Zhou VW, Goren A, Bernstein BE (2011) Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet 12(1):7–18. doi: 10.1038/nrg2905 CrossRefPubMedGoogle Scholar
  58. Zhou X, Fan LX, Sweeney WE Jr, Denu JM, Avner ED, Li X (2013) Sirtuin 1 inhibition delays cyst formation in autosomal-dominant polycystic kidney disease. J Clin Invest 123(7):3084–3098. doi: 10.1172/JCI64401 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Zhou X, Fan LX, Li K, Ramchandran R, Calvet JP, Li X (2014) SIRT2 regulates ciliogenesis and contributes to abnormal centrosome amplification caused by loss of polycystin-1. Hum Mol Genet 23(6):1644–1655. doi: 10.1093/hmg/ddt556 CrossRefPubMedGoogle Scholar
  60. Zhou X, Fan LX, Peters DJ, Trudel M, Bradner JE, Li X (2015) Therapeutic targeting of BET bromodomain protein, Brd4, delays cyst growth in ADPKD. Hum Mol Genet 24(14):3982–3993. doi: 10.1093/hmg/ddv136 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2016

Authors and Affiliations

  1. 1.Molecular Medicine Laboratory, Department of Life systemsSookmyung Women’s UniversitySeoulSouth Korea

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