IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26630-z.html
   My bibliography  Save this article

Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and transcriptomic variations

Author

Listed:
  • Xuemeng Zhou

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Tsz Wing Sam

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Ah Young Lee

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Danny Leung

    (The Hong Kong University of Science and Technology, Clear Water Bay
    The Hong Kong University of Science and Technology, Clear Water Bay)

Abstract

Polymorphic integrations of endogenous retroviruses (ERVs) have been previously detected in mouse and human genomes. While most are inert, a subset can influence the activity of the host genes. However, the molecular mechanism underlying how such elements affect the epigenome and transcriptome and their roles in driving intra-specific variation remain unclear. Here, by utilizing wildtype murine embryonic stem cells (mESCs) derived from distinct genetic backgrounds, we discover a polymorphic MMERGLN (GLN) element capable of regulating H3K27ac enrichment and transcription of neighboring loci. We demonstrate that this polymorphic element can enhance the neighboring Klhdc4 gene expression in cis, which alters the activity of downstream stress response genes. These results suggest that the polymorphic ERV-derived cis-regulatory element contributes to differential phenotypes from stimuli between mouse strains. Moreover, we identify thousands of potential polymorphic ERVs in mESCs, a subset of which show an association between proviral activity and nearby chromatin states and transcription. Overall, our findings elucidate the mechanism of how polymorphic ERVs can shape the epigenome and transcriptional networks that give rise to phenotypic divergence between individuals.

Suggested Citation

  • Xuemeng Zhou & Tsz Wing Sam & Ah Young Lee & Danny Leung, 2021. "Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and transcriptomic variations," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26630-z
    DOI: 10.1038/s41467-021-26630-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26630-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-26630-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yin Shen & Feng Yue & David F. McCleary & Zhen Ye & Lee Edsall & Samantha Kuan & Ulrich Wagner & Jesse Dixon & Leonard Lee & Victor V. Lobanenkov & Bing Ren, 2012. "A map of the cis-regulatory sequences in the mouse genome," Nature, Nature, vol. 488(7409), pages 116-120, August.
    2. Jeffrey T Leek & John D Storey, 2007. "Capturing Heterogeneity in Gene Expression Studies by Surrogate Variable Analysis," PLOS Genetics, Public Library of Science, vol. 3(9), pages 1-12, September.
    3. Özgen Deniz & Mamataz Ahmed & Christopher D. Todd & Ana Rio-Machin & Mark A. Dawson & Miguel R. Branco, 2020. "Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukaemia," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    4. John Arne Dahl & Inkyung Jung & Håvard Aanes & Gareth D. Greggains & Adeel Manaf & Mads Lerdrup & Guoqiang Li & Samantha Kuan & Bin Li & Ah Young Lee & Sebastian Preissl & Ingunn Jermstad & Mads Haugl, 2016. "Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition," Nature, Nature, vol. 537(7621), pages 548-552, September.
    5. Jeffrey A. Klein & Chantal M. Longo-Guess & Marlies P. Rossmann & Kevin L. Seburn & Ronald E. Hurd & Wayne N. Frankel & Roderick T. Bronson & Susan L. Ackerman, 2002. "The harlequin mouse mutation downregulates apoptosis-inducing factor," Nature, Nature, vol. 419(6905), pages 367-374, September.
    6. Marco Osterwalder & Iros Barozzi & Virginie Tissières & Yoko Fukuda-Yuzawa & Brandon J. Mannion & Sarah Y. Afzal & Elizabeth A. Lee & Yiwen Zhu & Ingrid Plajzer-Frick & Catherine S. Pickle & Momoe Kat, 2018. "Enhancer redundancy provides phenotypic robustness in mammalian development," Nature, Nature, vol. 554(7691), pages 239-243, February.
    7. Toshiyuki Matsui & Danny Leung & Hiroki Miyashita & Irina A. Maksakova & Hitoshi Miyachi & Hiroshi Kimura & Makoto Tachibana & Matthew C. Lorincz & Yoichi Shinkai, 2010. "Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET," Nature, Nature, vol. 464(7290), pages 927-931, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sophia Groh & Anna Viktoria Milton & Lisa Katherina Marinelli & Cara V. Sickinger & Angela Russo & Heike Bollig & Gustavo Pereira de Almeida & Andreas Schmidt & Ignasi Forné & Axel Imhof & Gunnar Scho, 2021. "Morc3 silences endogenous retroviruses by enabling Daxx-mediated histone H3.3 incorporation," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Markus Götz & Olivier Messina & Sergio Espinola & Jean-Bernard Fiche & Marcelo Nollmann, 2022. "Multiple parameters shape the 3D chromatin structure of single nuclei at the doc locus in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Poonam Dhillon & Kelly Ann Mulholland & Hailong Hu & Jihwan Park & Xin Sheng & Amin Abedini & Hongbo Liu & Allison Vassalotti & Junnan Wu & Katalin Susztak, 2023. "Increased levels of endogenous retroviruses trigger fibroinflammation and play a role in kidney disease development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Andrea Wilderman & Eva D’haene & Machteld Baetens & Tara N. Yankee & Emma Wentworth Winchester & Nicole Glidden & Ellen Roets & Jo Dorpe & Sandra Janssens & Danny E. Miller & Miranda Galey & Kari M. B, 2024. "A distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    5. repec:jss:jstsof:40:i14 is not listed on IDEAS
    6. Dafne Ibarra-Morales & Michael Rauer & Piergiuseppe Quarato & Leily Rabbani & Fides Zenk & Mariana Schulte-Sasse & Francesco Cardamone & Alejandro Gomez-Auli & Germano Cecere & Nicola Iovino, 2021. "Histone variant H2A.Z regulates zygotic genome activation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    7. Emanuele Aliverti & Kristian Lum & James E. Johndrow & David B. Dunson, 2021. "Removing the influence of group variables in high‐dimensional predictive modelling," Journal of the Royal Statistical Society Series A, Royal Statistical Society, vol. 184(3), pages 791-811, July.
    8. Seungchul Baek & Yen‐Yi Ho & Yanyuan Ma, 2020. "Using sufficient direction factor model to analyze latent activities associated with breast cancer survival," Biometrics, The International Biometric Society, vol. 76(4), pages 1340-1350, December.
    9. Shiran Bar & Dan Vershkov & Gal Keshet & Elyad Lezmi & Naama Meller & Atilgan Yilmaz & Ofra Yanuka & Malka Nissim-Rafinia & Eran Meshorer & Talia Eldar-Geva & Nissim Benvenisty, 2021. "Identifying regulators of parental imprinting by CRISPR/Cas9 screening in haploid human embryonic stem cells," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    10. Grigorios Fanourgakis & Laura Gaspa-Toneu & Pavel A. Komarov & Panagiotis Papasaikas & Evgeniy A. Ozonov & Sebastien A. Smallwood & Antoine H. F. M. Peters, 2025. "DNA methylation modulates nucleosome retention in sperm and H3K4 methylation deposition in early mouse embryos," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    11. Griffin, Maryclare & Hoff, Peter D., 2019. "Lasso ANOVA decompositions for matrix and tensor data," Computational Statistics & Data Analysis, Elsevier, vol. 137(C), pages 181-194.
    12. Jan-Renier Moonen & James Chappell & Minyi Shi & Tsutomu Shinohara & Dan Li & Maxwell R. Mumbach & Fan Zhang & Ramesh V. Nair & Joseph Nasser & Daniel H. Mai & Shalina Taylor & Lingli Wang & Ross J. M, 2022. "KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under laminar shear stress," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Delaram Pouyabahar & Tallulah Andrews & Gary D. Bader, 2025. "Interpretable single-cell factor decomposition using sciRED," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    14. Chee Ho H’ng & Shanika L. Amarasinghe & Boya Zhang & Hojin Chang & Xinli Qu & David R. Powell & Alberto Rosello-Diez, 2024. "Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    15. Michelle K. Y. Seah & Brenda Y. Han & Yan Huang & Louise J. H. Rasmussen & Andrina J. Stäubli & Judith Bello-Rodríguez & Andrew Chi-Ho Chan & Maxime Gasnier & Heike Wollmann & Ernesto Guccione & Danie, 2025. "Maternal PRDM10 activates essential genes for oocyte-to-embryo transition," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    16. Mark Reimers, 2010. "Making Informed Choices about Microarray Data Analysis," PLOS Computational Biology, Public Library of Science, vol. 6(5), pages 1-7, May.
    17. Raquel Rouco & Olimpia Bompadre & Antonella Rauseo & Olivier Fazio & Rodrigue Peraldi & Fabrizio Thorel & Guillaume Andrey, 2021. "Cell-specific alterations in Pitx1 regulatory landscape activation caused by the loss of a single enhancer," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    18. Leek Jeffrey T & Storey John D., 2011. "The Joint Null Criterion for Multiple Hypothesis Tests," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 10(1), pages 1-22, June.
    19. Ruohan Wang & Yumin Zheng & Zijian Zhang & Kailu Song & Erxi Wu & Xiaopeng Zhu & Tao P. Wu & Jun Ding, 2024. "MATES: a deep learning-based model for locus-specific quantification of transposable elements in single cell," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    20. Graeme J. Thorn & Christopher T. Clarkson & Anne Rademacher & Hulkar Mamayusupova & Gunnar Schotta & Karsten Rippe & Vladimir B. Teif, 2022. "DNA sequence-dependent formation of heterochromatin nanodomains," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    21. Nicoló Fusi & Oliver Stegle & Neil D Lawrence, 2012. "Joint Modelling of Confounding Factors and Prominent Genetic Regulators Provides Increased Accuracy in Genetical Genomics Studies," PLOS Computational Biology, Public Library of Science, vol. 8(1), pages 1-9, January.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26630-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.