Histone Methylome of the Human Parasite Schistosoma Mansoni

  • Ronaldo de Carvalho Augusto
  • Céline Cosseau
  • Christoph Grunau
Part of the RNA Technologies book series (RNATECHN)


The trematode Schistosoma mansoni belongs to the group of digenetic parasites which need obligatory multiple hosts to develop. They transit between hosts as free-swimming stages in fresh water ecosystems. They generate phenotypically different developmental stages throughout their lifecycle and receive hugly heterogenous environmental cues. Each developmental stage is characterized by specific posttranslational histone modifications, in particular methylations. The combination of the different marks result in stage specific chromatin structure that is essential for development, sexual biology and pathogenesis. Histone methylation also responds to environmental changes and seems to be involved in an adaptive reponse or adjustment to the environment. Histone methylation thus represent promising source of therapeutic targets. In this chapter we will present the state-of-the-art of how the dynamics of histone methylation are involved in multiple factors of the schistosome’s development, as well as what is still lacking for better understanding it.


Histone methylation Schistosomiasis Trematode Development 


  1. Ballante F, Reddy DR, Zhou NJ et al (2017) Structural insights of SmKDAC8 inhibitors: targeting Schistosoma epigenetics through a combined structure-based 3D QSAR, in vitro and synthesis strategy. Bioorg Med Chem 25:2105–2132CrossRefGoogle Scholar
  2. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381–395CrossRefGoogle Scholar
  3. Bao B, He Y, Tang D et al (2017) Inhibition of H3K27me3 histone demethylase activity prevents the proliferative regeneration of Zebrafish lateral line Neuromasts. Front Mol Neurosci 10:51CrossRefGoogle Scholar
  4. Barski A, Cuddapah S, Cui K et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837CrossRefGoogle Scholar
  5. Basch PF (1991) Schistosomes: development, reproduction, and host relations. Oxford University Press, New YorkGoogle Scholar
  6. Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412CrossRefGoogle Scholar
  7. Berriman M, Haas BJ, LoVerde PT et al (2009) The genome of the blood fluke Schistosoma mansoni. Nature 460:352–358CrossRefGoogle Scholar
  8. Boissier J, Grech-Angelini S, Webster BL et al (2016) Outbreak of urogenital schistosomiasis in Corsica (France): an epidemiological case study. Lancet Infect Dis 16:971–979CrossRefGoogle Scholar
  9. Brindley PJ, Sher A (1987) The chemotherapeutic effect of praziquantel against Schistosoma mansoni is dependent on host antibody response. J Immunol 139:215–220Google Scholar
  10. Cabezas-Cruz A, Lancelot J, Caby S et al (2014) Epigenetic control of gene function in schistosomes: a source of therapeutic targets? Front Genet 5:317CrossRefGoogle Scholar
  11. Chandler VL (2007) Paramutation: from maize to mice. Cell 128:641–645CrossRefGoogle Scholar
  12. Charlesworth D, Charlesworth B, Marais G (2005) Steps in the evolution of heteromorphic sex chromosomes. Heredity 95:118–128CrossRefGoogle Scholar
  13. Chevalier FD, Le Clec’h W, Eng N et al (2016) Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population. Int J Parasitol 46:417–424CrossRefGoogle Scholar
  14. Collins JJ, Wang B, Lambrus BG et al (2013) Adult somatic stem cells in the human parasite Schistosoma mansoni. Nature 494:476–479CrossRefGoogle Scholar
  15. Cosseau C, Grunau C (2011) Native chromatin immunoprecipitation. Methods Mol Biol Clifton NJ 791:195–212CrossRefGoogle Scholar
  16. Cosseau C, Wolkenhauer O, Padalino G et al (2017) (Epi)genetic inheritance in Schistosoma mansoni: a systems approach. Trends Parasitol 33:285–294CrossRefGoogle Scholar
  17. de Augusto RC, Tetreau G, Chan P et al (2017) Double impact: natural molluscicide for schistosomiasis vector control also impedes development of Schistosoma mansoni cercariae into adult parasites. PLoS Negl Trop Dis 11:e0005789CrossRefGoogle Scholar
  18. Dong X, Weng Z (2013) The correlation between histone modifications and gene expression. Epigenomics 5:113–116CrossRefGoogle Scholar
  19. Evertts AG, Manning AL, Wang X et al (2013) H4K20 methylation regulates quiescence and chromatin compaction. Mol Biol Cell 24:3025–3037CrossRefGoogle Scholar
  20. Fneich S, Théron A, Cosseau C et al (2016) Epigenetic origin of adaptive phenotypic variants in the human blood fluke Schistosoma mansoni. Epigenetics Chromatin 9:27CrossRefGoogle Scholar
  21. Gómez-Díaz E, Jordà M, Peinado MA et al (2012) Epigenetics of host–pathogen interactions: the road ahead and the road behind. PLoS Pathog 8:e1003007CrossRefGoogle Scholar
  22. Gu SG, Fire A (2010) Partitioning the C. elegans genome by nucleosome modification, occupancy, and positioning. Chromosoma 119:73–87CrossRefGoogle Scholar
  23. Harikumar A, Meshorer E (2015) Chromatin remodeling and bivalent histone modifications in embryonic stem cells. EMBO Rep 16:1609–1619CrossRefGoogle Scholar
  24. Howe FS, Fischl H, Murray SC et al (2017) Is H3K4me3 instructive for transcription activation? BioEssays News Rev Mol Cell Dev Biol 39:1–12CrossRefGoogle Scholar
  25. Jansma WB, Rogers SH, Liu CL et al (1977) Experimentally produced resistance of Schistosoma mansoni to hycanthone. Am J Trop Med Hyg 26:926–936CrossRefGoogle Scholar
  26. Jørgensen S, Schotta G, Sørensen CS (2013) Histone H4 lysine 20 methylation: key player in epigenetic regulation of genomic integrity. Nucleic Acids Res 41:2797–2806CrossRefGoogle Scholar
  27. Kharchenko PV, Alekseyenko AA, Schwartz YB et al (2011) Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471:480–485CrossRefGoogle Scholar
  28. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705CrossRefGoogle Scholar
  29. Landt SG, Marinov GK, Kundaje A et al (2012) ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia. Genome Res 22:1813–1831CrossRefGoogle Scholar
  30. Lepesant JMJ, Cosseau C, Boissier J et al (2012) Chromatin structural changes around satellite repeats on the female sex chromosome in Schistosoma mansoni and their possible role in sex chromosome emergence. Genome Biol 13:R14CrossRefGoogle Scholar
  31. Lindsay S (2007) Chromatin control of gene expression: the simplest model. Biophys J 92:1113CrossRefGoogle Scholar
  32. Lu Z, Sessler F, Holroyd N et al (2016) Schistosome sex matters: a deep view into gonad-specific and pairing-dependent transcriptomes reveals a complex gender interplay. Sci Rep 6:31150CrossRefGoogle Scholar
  33. Lv X, Han Z, Chen H et al (2016) A positive role for polycomb in transcriptional regulation via H4K20me1. Cell Res 26:529–542CrossRefGoogle Scholar
  34. Mikkelsen TS, Ku M, Jaffe DB et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448:553–560CrossRefGoogle Scholar
  35. Nicoglou A, Merlin F (2017) Epigenetics: a way to bridge the gap between biological fields. Stud Hist Philos Sci Part C Stud Hist Philos Biol Biomed Sci 66:73–82CrossRefGoogle Scholar
  36. Nightingale KP, O’Neill LP, Turner BM (2006) Histone modifications: signalling receptors and potential elements of a heritable epigenetic code. Curr Opin Genet Dev 16:125–136CrossRefGoogle Scholar
  37. Oda H, Okamoto I, Murphy N et al (2009) Monomethylation of histone H4-lysine 20 is involved in chromosome structure and stability and is essential for mouse development. Mol Cell Biol 29:2278–2295CrossRefGoogle Scholar
  38. Padalino G, Ferla S, Brancale A et al (2018) Combining bioinformatics, cheminformatics, functional genomics and whole organism approaches for identifying epigenetic drug targets in Schistosoma mansoni. Int J Parasitol Drugs Drug Resist 8:559–570CrossRefGoogle Scholar
  39. Pellegrino J, Katz N, Oliveira CA (1969) Further clinical trials with hycanthone, a new antischistosomal agent. Am J Trop Med Hyg 18:924–929CrossRefGoogle Scholar
  40. Pereira ASA, Amaral MS, Vasconcelos EJR et al (2018) Inhibition of histone methyltransferase EZH2 in Schistosoma mansoni in vitro by GSK343 reduces egg laying and decreases the expression of genes implicated in DNA replication and noncoding RNA metabolism. PLoS Negl Trop Dis 12:e0006873CrossRefGoogle Scholar
  41. Perrin C, Lepesant JMJ, Roger E et al (2013) Schistosoma mansoni Mucin gene (SmPoMuc) expression: epigenetic control to shape adaptation to a new host. PLoS Pathog 9:e1003571CrossRefGoogle Scholar
  42. Picard MAL, Boissier J, Roquis D et al (2016) Sex-biased transcriptome of Schistosoma mansoni: host-parasite interaction, genetic determinants and epigenetic regulators are associated with sexual differentiation. PLoS Negl Trop Dis 10:e0004930CrossRefGoogle Scholar
  43. Protasio AV, Tsai IJ, Babbage A et al (2012) A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni. PLoS Negl Trop Dis 6:e1455CrossRefGoogle Scholar
  44. Roquis D, Lepesant JMJ, Villafan E et al (2014) Exposure to hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni. Front Genet 5:207CrossRefGoogle Scholar
  45. Roquis D, Lepesant JMJ, Picard MAL et al (2015) The epigenome of Schistosoma mansoni provides insight about how Cercariae poise transcription until infection. PLoS Negl Trop Dis 9:e0003853CrossRefGoogle Scholar
  46. Roquis D, Rognon A, Chaparro C et al (2016) Frequency and mitotic heritability of epimutations in Schistosoma mansoni. Mol Ecol 25:1741–1758CrossRefGoogle Scholar
  47. Roquis D, Taudt A, Padalino G et al (2018) Histone methylation changes are required for life cycle progression in the human parasite Schistosoma mansoni. PLoS Pathog 14:e1007066CrossRefGoogle Scholar
  48. Rosi D, Peruzzotti G, Dennis EW et al (1965) A new, active metabolite of ‘Miracil D’. Nature 208:1005–1006CrossRefGoogle Scholar
  49. Steinmann P, Keiser J, Bos R et al (2006) Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 6:411–425CrossRefGoogle Scholar
  50. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45CrossRefGoogle Scholar
  51. Taube JH, Barton MC (2006) Chromatin and regulation of gene expression. In: Ma J (ed) Gene expression and regulation. Springer, New York, NY, pp 95–109CrossRefGoogle Scholar
  52. Taudt A, Nguyen MA, Heinig M et al (2016) chromstaR: tracking combinatorial chromatin state dynamics in space and time.
  53. Valentim CLL, Cioli D, Chevalier FD et al (2013) Genetic and molecular basis of drug resistance and species-specific drug action in Schistosome parasites. Science 342:1385–1389CrossRefGoogle Scholar
  54. Vielle A, Lang J, Dong Y et al (2012) H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation. PLoS Genet 8:e1002933CrossRefGoogle Scholar
  55. Wang Z, Zang C, Rosenfeld JA et al (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40:897–903CrossRefGoogle Scholar
  56. Wang B, Collins JJ, Newmark PA (2013) Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni. elife 2:e00768CrossRefGoogle Scholar
  57. Zentner GE, Henikoff S (2013) Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 20:259–266CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ronaldo de Carvalho Augusto
    • 1
    • 2
    • 3
    • 4
  • Céline Cosseau
    • 1
    • 2
    • 3
    • 4
  • Christoph Grunau
    • 1
    • 2
    • 3
    • 4
  1. 1.University of MontpellierMontpellierFrance
  2. 2.CNRSPerpignanFrance
  3. 3.IFremerMontpellierFrance
  4. 4.University of Perpignan Via DomitiaPerpignanFrance

Personalised recommendations