Skip to main content
Log in

Mining histone methyltransferases and demethylases from whole genome sequence

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Epigenetic regulation through post-translational modification of histones, especially methylation, is well conserved in evolution. Although there are several insect genomes sequenced, an analysis with a focus on their epigenetic repertoire is limited. We have utilized a novel work-flow to identify one or more domains as high-priority domain (HPD), if present in at least 50% of the genes of a given functional class in the reference genome, namely, that of Drosophila melanogaster. Based on this approach, we have mined histone methyltransferases and demethylases from the whole genome sequence of Aedes aegypti (Diptera), the pea aphid Acyrthosiphon pisum, the triatomid bug Rhodnius prolixus (Hemiptera), the honeybee Apis mellifera (Hymenoptera), the silkworm Bombyx mori (Lepidoptera) and the red flour beetle Tribolium castaneum (Coleoptera). We identified 38 clusters consisting of arginine methyltransferases, lysine methyltransferases and demethylases using OrthoFinder, and the presence of HPD was queried in these sequences using InterProScan. This approach led us to identify putative novel members and currently inaccurate ones. Other than the high-priority domains, these proteins contain shared and unique domains that can mediate protein–protein interaction. Phylogenetic analysis indicates that there is different extent of protein sequence similarity; average similarity between histone lysine methyltransferases varies from 41% (for active mark) to 48% (for repressive mark), arginine methyltransferases is 51%, and demethylases is 52%. The method utilized here facilitates reliable identification of desired functional class in newly sequenced genomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

Abbreviations

HPD:

high-priority domain

KMT:

lysine methyltransferases

PRMT:

protein arginine methyltransferases

PTM:

post-translational modification

References

  • Alkema MJ, Bronk M, Verhoeven E, Otte A, van ‘t Veer LJ, Berns A and van Lohuizen M 1997 Identification of Bmil-interacting proteins as constituents of a multimeric mammalian Polycomb complex. Genes Dev. 11 226–240

    CAS  PubMed  Google Scholar 

  • Bannister AJ and Kouzarides T 2011 Regulation of chromatin by histone modifications. Cell Res. 21 381–395

    CAS  PubMed  PubMed Central  Google Scholar 

  • Black JC, Van RC and Whetstine JR 2012 Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol. Cell 48 491–507

    CAS  PubMed  Google Scholar 

  • Brown DA, Di Cerbo V, Feldmann A, Ahn J, Ito S, Blackledge NP, Nakayama M, McClellan M, Dimitrova E, Turberfield AH and Long HK 2017 The SET1 complex selects actively transcribed target genes via multivalent interaction with CpG island chromatin. Cell Rep. 20 2313–2327

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cloos PAC, Christensen J, Agger K and Helin K 2008 Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev. 22 1115–1140

    CAS  Google Scholar 

  • Clough E, Tedeschi T and Hazelrigg T 2014 Epigenetic regulation of oogenesis and germ stem cell maintenance by the Drosophila histone methyltransferase Eggless/dSetDB1. Dev. Biol. 388 181–191

    CAS  PubMed  PubMed Central  Google Scholar 

  • Colmenares SU, Swenson JM, Langley SA, Kennedy C, Costes SV and Karpen GH 2017 Drosophila histone demethylase KDM4a has enzymatic and non-enzymatic roles in controlling heterochromatin integrity. Dev. Cell 42 156–169

    CAS  PubMed  PubMed Central  Google Scholar 

  • Elgin SCR and Reuter G 2013 Position-effect variegation, heterochromatin formation and gene silencing in Drosophila. Cold Spring Harb. Perspect. Biol. 5 a017780

    PubMed  PubMed Central  Google Scholar 

  • Emms DM and Kelly S 2015 OrthoFinder: solving fundamental biases in whole genome comparisons dramatically improves orthogroup inference accuracy. Genome Biol. 16 157

    PubMed  PubMed Central  Google Scholar 

  • Escandón-Vargas K, Muñoz-Zuluaga CA and Salazar L 2017. Blood-feeding of Rhodnius prolixus. Biomédica 37 299–302

    PubMed  Google Scholar 

  • Fuhrmann J and Thompson PR 2016 Protein arginine methylation and citrullination in epigenetic regulation. ACS Chem. Biol. 11 654–668

    CAS  PubMed  Google Scholar 

  • Gaudet P, Livstone MS, Lewis SE and Thomas PD 2010 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief. Bioinform. 12 449–462

    Google Scholar 

  • Gilbert C, Schaack S, Pace II JK, Brindley PJ and Feschotte C 2010 A role for host–parasite interactions in the horizontal transfer of DNA transposons across animal phyla. Nature 464 1347–1350

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gillette TG and Hill JA 2015 Readers, writers, and erasers: chromatin as the whiteboard of heart disease. Circ. Res. 116 1245–1253

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hyun K, Jeon, J, Park K and Kim J 2017 Writing, erasing and reading histone lysine methylations. Exp. Mol. Med. 49 e324

    CAS  Google Scholar 

  • Imai K and Ochiai K 2011 Role of histone modification on transcriptional regulation and HIV-1 gene expression: possible mechanisms of periodontal diseases in AIDS progression. J. Oral Sci. 53 1–13

    CAS  PubMed  Google Scholar 

  • International Aphid Genomics Consortium 2010 Genome sequence of the pea aphid Acyrthosiphon pisum. PLoS Biol. 8 e1000313

    Google Scholar 

  • Janssen A, Colmenares SU, Lee T and Karpen GH 2019 Timely double-strand break repair and pathway choice in pericentromeric heterochromatin depend on the histone demethylase dKDM4A. Genes Dev. 33 103–115

    CAS  Google Scholar 

  • Jones P, Binns D, Chang Hsin-Yu, Fraser M, Li W, McAnulla C, McWilliam H, Maslen J, Mitchell A, Nuka G, Pesseat S, Quinn AF, Sangrador-Vegas A, Scheremetjew M, Yong Siew-Yit, Lopez R and Hunter S 2014 InterProScan 5: genome-scale protein function classification. Bioinformatics 30 1236–1234

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kang I, Choi Y, Jung S, Lim JY, Lee D, Gupta S, Moon W and Shin C 2018 Identification of target genes regulated by the Drosophila histone methyltransferase Eggless reveals a role of Decapentaplegic in apoptotic signalling. Sci. Rep. 8 7123

    PubMed  PubMed Central  Google Scholar 

  • Katoh K and Standley DM 2013 MAFFT multiple sequence alignment software version7: improvements in performance and usability. Mol. Biol. Evol. 30 772–780

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JH, Yoo BC, Yang WS, Kim E, Hong S and Cho JY 2016 The role of protein arginine methyltransferases in inflammatory responses. Mediat. Inflamm. 1 11

    Google Scholar 

  • Kim T and Buratowski S 2007 Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation. J. Biol. Chem. 282 20827–20835

    CAS  Google Scholar 

  • Kizer KO, Phatnani HP, Shibata Y, Hall H, Greenleaf AL and Strahl BD 2005 A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol. Cell Biol. 25 3305–3316

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klose RJ, Kallin EM and Zhang Y 2006 JmjC-domain-containing proteins and histone demethylation. Nat. Rev. Genet. 7 715–727

    CAS  PubMed  Google Scholar 

  • Kooistra SM and Helin K 2012 Molecular mechanisms and potential functions of histone demethylases. Nat. Rev. Mol. Cell Biol. 13 297–311

    Google Scholar 

  • Mohan M, Herz HM, Smith ER, Zhang Y, Jackson J, Washburn MP, Florens L, Eissenberg JC and Shilatifard A 2011 The COMPASS family of H3K4 methylases in Drosophila. Mol. Cell. Biol. 31 4310–4318

    CAS  PubMed  PubMed Central  Google Scholar 

  • Motamedi H, Shafiee A, Cai SJ, Streicher SL, Arison BH and Miller RR 1996 Characterization of methyltransferase and hydroxylase genes involved in the biosynthesis of the immunosuppressants FK506 and FK520. J. Bacteriol. 178 5243–5248

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mukherjee K, Twyman RM and Vilcinskas A 2015 Insects as models to study the epigenetic basis of disease. Prog. Biophys. Mol. Biol. 118 69–78

    CAS  PubMed  Google Scholar 

  • Ogawa K and Miura T 2014 Aphid polyphenisms: trans-generational developmental regulation through viviparity. Front. Physiol. 5 1

    PubMed  PubMed Central  Google Scholar 

  • Olsen CA 2012 Expansion of the lysine acylation landscape. Angew. Chem. Int. Ed. 51 3755–3756

    CAS  Google Scholar 

  • Paixão ES, Teixeira MG and Rodrigues LC 2017 Zika, chikungunya and dengue: the causes and threats of new and re-emerging arboviral diseases. BMJ Glob. Health 3 e000530

    Google Scholar 

  • Paradis E, Claude J and Strimmer K 2004 APE: analyses of phylogenetics and evolution in R language. Bioinformatics 20 289–290

    CAS  PubMed  Google Scholar 

  • Petruk S, Sedkov Y, Smith S, Tillib S, Kraevski V, Nakamura T, Canaani E, Croce CM and Mazo A 2001: Trithorax and dCBP acting in a complex to maintain expression of a homeotic gene. Science 294 1331–1334

    CAS  PubMed  Google Scholar 

  • Rangan P, Malone CD, Navarro C, Newbold SP, Hayes PS, Sachidanandam R, Hannon GJ and Lehmann R 2011 piRNA production requires heterochromatin formation in Drosophila. Curr Biol. 21 1373–1379

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD and Jenuwein T 2000 Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406 593–599

    CAS  PubMed  Google Scholar 

  • Rothbart SB and Strahl BD 2014 Interpreting the language of histone and DNA modifications. Biochem. Biophys. Acta Gene Regul. Mech. 1839 627

    CAS  Google Scholar 

  • Rozovskaia T, Tillib S, Smith S, Sedkov Y, Rozenblatt-Rosen O, Petruk S, Yano T, Nakamura T, Ben-Simchon L, Gildea J and Croce CM 1999 Trithorax and ASH1 interact directly and associate with the trithorax group-responsive bxd region of the ultrabithorax promoter. Mol. Cell. Biol. 19 6441–6447

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sewalt RG, van der Vlag J, Gunster MJ, Hamer KM, den Blaauwen JL, Satijn DP, Hendrix T, van Driel R and Otte AP 1998 Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes. Mol. Cell. Biol. 18 3586–3595

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shi Y and Whetstine JR 2007 Dynamic regulation of histone lysine methylation by demethylases. Mol. Cell 25 1–14

    CAS  PubMed  Google Scholar 

  • Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA and Shi Y 2004 Histone demethylation mediated by the nuclear amine oxidase homolog LSD. Cell 119 941–953

    CAS  PubMed  Google Scholar 

  • Sims RJ 3rd, Nishioka K and Reinberg D 2003 Histone lysine methylation: a signature for chromatin function. Trends Genet. 19 629–639

    CAS  PubMed  Google Scholar 

  • Smolko A, Shapiro-Kulnane L and Salz H 2018 H3K9 methylation maintains female identity in Drosophila germ cells. Nat. Commun. 9 4155

    PubMed  PubMed Central  Google Scholar 

  • Stabell M, Larsson J, Reidunn BA and Lambertsson A 2007 Drosophila dSet2 functions in H3-K36 methylation and is required for development. Biochem. Biophys. Res. Commun. 359 784–789

    CAS  PubMed  Google Scholar 

  • Strahl BD and Allis CD 2000 The language of covalent histone modifications. Nature 403 41–45

    CAS  PubMed  Google Scholar 

  • The UniProt Consortium 2017 UniProt: the universal protein knowledgebase. Nucleic Acids Res. 45 D158–D169

    Google Scholar 

  • Tsai C, Shi Y and Tainer JA 2014 How substrate specificity is imposed on a histone demethylase—lessons from KDM2A. Genes Dev. (CSHP) 28 1735–1738

    CAS  Google Scholar 

  • Tsurumi A, Dutta P, Yan SJ, Shang R and Li WX 2013 Drosophila Kdm4 demethylases in histone H3 lysine 9 demethylation and ecdysteroid signaling. Sci. Rep. 3 2894

    PubMed  PubMed Central  Google Scholar 

  • Vellichirammal NN, Gupta P, Hall TA and Brisson JA 2017 Ecdysone signaling underlies the pea aphid transgenerational wing polyphenism. Proc. Natl. Acad. Sci. 114 1419–1423

    CAS  Google Scholar 

  • Verma A, Maini J, Jain S, Ghasemi M, Kohli S and Brahmachari V. Epigenetic regulation and transcriptional memory in development; an example of selection facilitating prudence (in press)

  • Wang YC, Suzanne EP and Loring JP 2014 Protein post-translational modifications and regulation of pluripotency in human stem cells. Cell Res. 24 143–160

    PubMed  Google Scholar 

  • Wang Z, Yin H, Lau CS and Lu Q 2016 Histone post translational modifications of CD4+T cell in autoimmune diseases. Int. J. Mol. Sci 17 1547

    PubMed Central  Google Scholar 

  • Wei H, Mundade R, Lange KC, Lu T 2014 Protein arginine methylation of non-histone proteins and its role in diseases. Cell Cycle 13 32–41

    PubMed  Google Scholar 

  • Wozniak GG and Strahl BD 2014 Hitting the ‘mark’: interpreting lysine methylation in the context of active transcription. Biochim. Biophys. Acta Gene Regul. Mech. 1839 1353–1361

    CAS  Google Scholar 

  • Yang CH and Pospisilik AJ 2019 Polyphenism—a window into gene–environment interactions and phenotypic plasticity. Front. Genet. 10 132

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang SY, Chang YC, Wan YH, Whitworth C, Baxter EM, Primus S, Pi H, Van Doren M 2017 Control of a novel spermatocyte-promoting factor by the male germline sex determination factor Phf7 of Drosophila melanogaster. Genetics 206 1939–1949

    CAS  PubMed  PubMed Central  Google Scholar 

  • Young LC, McDonald DW and Hendzel MJ 2013 Kdm4b histone demethylase is a DNA damage response protein and confers a survival advantage following γ-irradiation. J. Biol. Chem. 28 21376–21388

    Google Scholar 

  • Zhao Y and Garcia BA 2015 Comprehensive catalog of currently documented histone modification. Cold Spring Harb. Perspect. Biol. 7 a025064

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the funding for the work through research grant to VB from the Council for Scientific and Industrial Research (CSIR), (EpiHeD: BSC0118/2012-17) and SERB No. 60 (0102)/12/EMR-II), India. We acknowledge DBT Bioinformatics facility at ACBR and the UGC SAP-II support. PG acknowledges CSIR; SK and AN acknowledge University Grants Commission, India, for support through Senior Research Fellowship and D.S. Kothari Post-doctoral fellowship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vani Brahmachari.

Additional information

This article is part of the Topical Collection: Chromatin Biology and Epigenetics.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gulati, P., Kohli, S., Narang, A. et al. Mining histone methyltransferases and demethylases from whole genome sequence. J Biosci 45, 9 (2020). https://doi.org/10.1007/s12038-019-9982-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s12038-019-9982-3

Keywords