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Heterochromatin is a quantitative trait associated with spontaneous epiallele formation

Author

Listed:
  • Yinwen Zhang

    (University of Georgia)

  • Hosung Jang

    (University of Georgia)

  • Rui Xiao

    (University of Georgia)

  • Ioanna Kakoulidou

    (Technical University of Munich)

  • Robert S. Piecyk

    (Technical University of Munich)

  • Frank Johannes

    (Technical University of Munich
    Technical University of Munich)

  • Robert J. Schmitz

    (University of Georgia
    Technical University of Munich)

Abstract

Epialleles are meiotically heritable variations in expression states that are independent from changes in DNA sequence. Although they are common in plant genomes, their molecular origins are unknown. Here we show, using mutant and experimental populations, that epialleles in Arabidopsis thaliana that result from ectopic hypermethylation are due to feedback regulation of pathways that primarily function to maintain DNA methylation at heterochromatin. Perturbations to maintenance of heterochromatin methylation leads to feedback regulation of DNA methylation in genes. Using single base resolution methylomes from epigenetic recombinant inbred lines (epiRIL), we show that epiallelic variation is abundant in euchromatin, yet, associates with QTL primarily in heterochromatin regions. Mapping three-dimensional chromatin contacts shows that genes that are hotspots for ectopic hypermethylation have increases in contact frequencies with regions possessing H3K9me2. Altogether, these data show that feedback regulation of pathways that have evolved to maintain heterochromatin silencing leads to the origins of spontaneous hypermethylated epialleles.

Suggested Citation

  • Yinwen Zhang & Hosung Jang & Rui Xiao & Ioanna Kakoulidou & Robert S. Piecyk & Frank Johannes & Robert J. Schmitz, 2021. "Heterochromatin is a quantitative trait associated with spontaneous epiallele formation," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27320-6
    DOI: 10.1038/s41467-021-27320-6
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    References listed on IDEAS

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    1. Claude Becker & Jörg Hagmann & Jonas Müller & Daniel Koenig & Oliver Stegle & Karsten Borgwardt & Detlef Weigel, 2011. "Spontaneous epigenetic variation in the Arabidopsis thaliana methylome," Nature, Nature, vol. 480(7376), pages 245-249, December.
    2. Matthew D. Schultz & Yupeng He & John W. Whitaker & Manoj Hariharan & Eran A. Mukamel & Danny Leung & Nisha Rajagopal & Joseph R. Nery & Mark A. Urich & Huaming Chen & Shin Lin & Yiing Lin & Inkyung J, 2015. "Human body epigenome maps reveal noncanonical DNA methylation variation," Nature, Nature, vol. 523(7559), pages 212-216, July.
    3. Meilina Ong-Abdullah & Jared M. Ordway & Nan Jiang & Siew-Eng Ooi & Sau-Yee Kok & Norashikin Sarpan & Nuraziyan Azimi & Ahmad Tarmizi Hashim & Zamzuri Ishak & Samsul Kamal Rosli & Fadila Ahmad Malike , 2015. "Loss of Karma transposon methylation underlies the mantled somaclonal variant of oil palm," Nature, Nature, vol. 525(7570), pages 533-537, September.
    4. James P. Jackson & Anders M. Lindroth & Xiaofeng Cao & Steven E. Jacobsen, 2002. "Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase," Nature, Nature, vol. 416(6880), pages 556-560, April.
    5. Lianna M. Johnson & Jiamu Du & Christopher J. Hale & Sylvain Bischof & Suhua Feng & Ramakrishna K. Chodavarapu & Xuehua Zhong & Giuseppe Marson & Matteo Pellegrini & David J. Segal & Dinshaw J. Patel , 2014. "SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation," Nature, Nature, vol. 507(7490), pages 124-128, March.
    6. Pilar Cubas & Coral Vincent & Enrico Coen, 1999. "An epigenetic mutation responsible for natural variation in floral symmetry," Nature, Nature, vol. 401(6749), pages 157-161, September.
    7. Shawn J. Cokus & Suhua Feng & Xiaoyu Zhang & Zugen Chen & Barry Merriman & Christian D. Haudenschild & Sriharsa Pradhan & Stanley F. Nelson & Matteo Pellegrini & Steven E. Jacobsen, 2008. "Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning," Nature, Nature, vol. 452(7184), pages 215-219, March.
    8. Julie A. Law & Jiamu Du & Christopher J. Hale & Suhua Feng & Krzysztof Krajewski & Ana Marie S. Palanca & Brian D. Strahl & Dinshaw J. Patel & Steven E. Jacobsen, 2013. "Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1," Nature, Nature, vol. 498(7454), pages 385-389, June.
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