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Isoform-specific and ubiquitination dependent recruitment of Tet1 to replicating heterochromatin modulates methylcytosine oxidation

Author

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  • María Arroyo

    (Technical University of Darmstadt)

  • Florian D. Hastert

    (Technical University of Darmstadt
    Section AIDS and newly emerging pathogens, Paul Ehrlich Institute)

  • Andreas Zhadan

    (Technical University of Darmstadt)

  • Florian Schelter

    (Ludwig Maximilians University)

  • Susanne Zimbelmann

    (Technical University of Darmstadt)

  • Cathia Rausch

    (Technical University of Darmstadt
    University of Luxembourg)

  • Anne K. Ludwig

    (Technical University of Darmstadt
    University Hospital Heidelberg)

  • Thomas Carell

    (Ludwig Maximilians University)

  • M. Cristina Cardoso

    (Technical University of Darmstadt)

Abstract

Oxidation of the epigenetic DNA mark 5-methylcytosine by Tet dioxygenases is an established route to diversify the epigenetic information, modulate gene expression and overall cellular (patho-)physiology. Here, we demonstrate that Tet1 and its short isoform Tet1s exhibit distinct nuclear localization during DNA replication resulting in aberrant cytosine modification levels in human and mouse cells. We show that Tet1 is tethered away from heterochromatin via its zinc finger domain, which is missing in Tet1s allowing its targeting to these regions. We find that Tet1s interacts with and is ubiquitinated by CRL4(VprBP). The ubiquitinated Tet1s is then recognized by Uhrf1 and recruited to late replicating heterochromatin. This leads to spreading of 5-methylcytosine oxidation to heterochromatin regions, LINE 1 activation and chromatin decondensation. In summary, we elucidate a dual regulation mechanism of Tet1, contributing to the understanding of how epigenetic information can be diversified by spatio-temporal directed Tet1 catalytic activity.

Suggested Citation

  • María Arroyo & Florian D. Hastert & Andreas Zhadan & Florian Schelter & Susanne Zimbelmann & Cathia Rausch & Anne K. Ludwig & Thomas Carell & M. Cristina Cardoso, 2022. "Isoform-specific and ubiquitination dependent recruitment of Tet1 to replicating heterochromatin modulates methylcytosine oxidation," Nature Communications, Nature, vol. 13(1), pages 1-28, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32799-8
    DOI: 10.1038/s41467-022-32799-8
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    References listed on IDEAS

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    1. Henry D. Herce & Wen Deng & Jonas Helma & Heinrich Leonhardt & M. Cristina Cardoso, 2013. "Visualization and targeted disruption of protein interactions in living cells," Nature Communications, Nature, vol. 4(1), pages 1-8, December.
    2. Jafar Sharif & Masahiro Muto & Shin-ichiro Takebayashi & Isao Suetake & Akihiro Iwamatsu & Takaho A. Endo & Jun Shinga & Yoko Mizutani-Koseki & Tetsuro Toyoda & Kunihiro Okamura & Shoji Tajima & Kohzo, 2007. "The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA," Nature, Nature, vol. 450(7171), pages 908-912, December.
    3. Myunggon Ko & Jungeun An & Hozefa S. Bandukwala & Lukas Chavez & Tarmo Äijö & William A. Pastor & Matthew F. Segal & Huiming Li & Kian Peng Koh & Harri Lähdesmäki & Patrick G. Hogan & L. Aravind & Anj, 2013. "Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX," Nature, Nature, vol. 497(7447), pages 122-126, May.
    4. Teresa A. Soucy & Peter G. Smith & Michael A. Milhollen & Allison J. Berger & James M. Gavin & Sharmila Adhikari & James E. Brownell & Kristine E. Burke & David P. Cardin & Stephen Critchley & Courtne, 2009. "An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer," Nature, Nature, vol. 458(7239), pages 732-736, April.
    5. Corella S. Casas-Delucchi & Alessandro Brero & Hans-Peter Rahn & Irina Solovei & Anton Wutz & Thomas Cremer & Heinrich Leonhardt & M. Cristina Cardoso, 2011. "Histone acetylation controls the inactive X chromosome replication dynamics," Nature Communications, Nature, vol. 2(1), pages 1-11, September.
    6. Xiaoli Liu & Qinqin Gao & Pishun Li & Qian Zhao & Jiqin Zhang & Jiwen Li & Haruhiko Koseki & Jiemin Wong, 2013. "UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9," Nature Communications, Nature, vol. 4(1), pages 1-13, June.
    7. V. O. Chagin & C. S. Casas-Delucchi & M. Reinhart & L. Schermelleh & Y. Markaki & A. Maiser & J. J. Bolius & A. Bensimon & M. Fillies & P. Domaing & Y. M. Rozanov & H. Leonhardt & M. C. Cardoso, 2016. "4D Visualization of replication foci in mammalian cells corresponding to individual replicons," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
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    1. Kosuke Yamaguchi & Xiaoying Chen & Brianna Rodgers & Fumihito Miura & Pavel Bashtrykov & Frédéric Bonhomme & Catalina Salinas-Luypaert & Deis Haxholli & Nicole Gutekunst & Bihter Özdemir Aygenli & Lau, 2024. "Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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