علوم وتكنولوجيا

A nowheretohide mechanism ensures complete piRNAdirected DNA methylation

  • Aravin, A. A., Sachidanandam, R., Girard, A., Fejes-Toth, K. & Hannon, G. J. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316, 744–747 (2007).

    Article
    ADS
    CAS
    PubMed

    Google Scholar

  • Carmell, M. A. et al. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev. Cell 12, 503–514 (2007).

    Article
    CAS
    PubMed

    Google Scholar

  • Kuramochi-Miyagawa, S. et al. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 22, 908–917 (2008).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Dias Mirandela, M. et al. Two-factor authentication underpins the precision of the piRNA pathway. Nature 634, 979–985 (2024).

    Article
    ADS
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • De Fazio, S. et al. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 480, 259–263 (2011).

    Article
    ADS
    PubMed

    Google Scholar

  • Schopp, T. et al. TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing. Nat. Commun. 11, 3739 (2020).

    Article
    ADS
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Krull, S. et al. Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion. EMBO J. 29, 1659–1673 (2010).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Walsh, C. P., Chaillet, J. R. & Bestor, T. H. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet. 20, 116–117 (1998).

    Article
    CAS
    PubMed

    Google Scholar

  • Greenberg, M. V. C. & Bourc’his, D. The diverse roles of DNA methylation in mammalian development and disease. Nat. Rev. Mol. Cell Biol. 20, 590–607 (2019).

    Article
    CAS
    PubMed

    Google Scholar

  • Kafri, T. et al. Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev. 6, 705–714 (1992).

    Article
    CAS
    PubMed

    Google Scholar

  • Monk, M., Boubelik, M. & Lehnert, S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development 99, 371–382 (1987).

    Article
    CAS
    PubMed

    Google Scholar

  • Seisenberger, S. et al. The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol. Cell 48, 849–862 (2012).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Bourc’his, D. & Bestor, T. H. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431, 96–99 (2004).

    Article
    ADS
    PubMed

    Google Scholar

  • Ozata, D. M., Gainetdinov, I., Zoch, A., O’Carroll, D. & Zamore, P. D. PIWI-interacting RNAs: small RNAs with big functions. Nat. Rev. Genet. 20, 89–108 (2019).

    Article
    CAS
    PubMed

    Google Scholar

  • Aravin, A. A. et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 31, 785–799 (2008).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Molaro, A. et al. Two waves of de novo methylation during mouse germ cell development. Genes Dev. 28, 1544–1549 (2014).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Barau, J. et al. The DNA methyltransferase DNMT3C protects male germ cells from transposon activity. Science 354, 909–912 (2016).

    Article
    ADS
    CAS
    PubMed

    Google Scholar

  • Jain, D. et al. rahu Is a mutant allele of Dnmt3c, encoding a DNA methyltransferase homolog required for meiosis and transposon repression in the mouse male germline. PLoS Genet. 13, e1006964 (2017).

    Article
    PubMed
    PubMed Central

    Google Scholar

  • Zoch, A. et al. SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation. Nature 584, 635–639 (2020).

    Article
    ADS
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Zoch, A. et al. C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line. Mol. Cell https://doi.org/10.1016/j.molcel.2024.01.014 (2024).

    Article
    PubMed
    PubMed Central

    Google Scholar

  • Yoshioka, H., McCarrey, J. R. & Yamazaki, Y. Dynamic nuclear organization of constitutive heterochromatin during fetal male germ cell development in mice. Biol. Reprod. 80, 804–812 (2009).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Santos-Rosa, H. et al. Active genes are tri-methylated at K4 of histone H3. Nature 419, 407–411 (2002).

    Article
    ADS
    CAS
    PubMed

    Google Scholar

  • Vasiliauskaite, L. et al. A MILI-independent piRNA biogenesis pathway empowers partial germline reprogramming. Nat. Struct. Mol. Biol. 24, 604–606 (2017).

    Article
    CAS
    PubMed

    Google Scholar

  • Cordes, V. C., Hase, M. E. & Muller, L. Molecular segments of protein Tpr that confer nuclear targeting and association with the nuclear pore complex. Exp. Cell Res. 245, 43–56 (1998).

    Article
    CAS
    PubMed

    Google Scholar

  • Cordes, V. C., Reidenbach, S., Rackwitz, H. R. & Franke, W. W. Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments. J. Cell Biol. 136, 515–529 (1997).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Mitchell, P. J. & Cooper, C. S. The human tpr gene encodes a protein of 2094 amino acids that has extensive coiled-coil regions and an acidic C-terminal domain. Oncogene 7, 2329–2333 (1992).

    CAS
    PubMed

    Google Scholar

  • Singh, D. et al. The molecular architecture of the nuclear basket. Cell 187, 5267–5281.e13 (2024).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Nakano, H., Funasaka, T., Hashizume, C. & Wong, R. W. Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis. J. Biol. Chem. 285, 10841–10849 (2010).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Bartlett, B. M. et al. TPR is required for cytoplasmic chromatin fragment formation during senescence. eLife https://doi.org/10.7554/eLife.101702 (2024).

  • Coyle, J. H., Bor, Y. C., Rekosh, D. & Hammarskjold, M. L. The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA 17, 1344–1356 (2011).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Pastor, W. A. et al. MORC1 represses transposable elements in the mouse male germline. Nat. Commun. 5, 5795 (2014).

    Article
    ADS
    CAS
    PubMed

    Google Scholar

  • Vasiliauskaite, L. et al. Defective germline reprogramming rewires the spermatogonial transcriptome. Nat. Struct. Mol. Biol. 25, 394–404 (2018).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Watanabe, T. et al. Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332, 848–852 (2011).

    Article
    ADS
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Di Giacomo, M. et al. Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis. Mol. Cell 50, 601–608 (2013).

    Article
    PubMed

    Google Scholar

  • Carrieri, C. et al. A transit-amplifying population underpins the efficient regenerative capacity of the testis. J. Exp. Med. 214, 1631–1641 (2017).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Wang, H. et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910–918 (2013).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Di Giacomo, M., Comazzetto, S., Sampath, S. C., Sampath, S. C. & O’Carroll, D. G9a co-suppresses LINE1 elements in spermatogonia. Epigenetics Chromatin 7, 24 (2014).

    Article
    PubMed
    PubMed Central

    Google Scholar

  • Pandey, R. R. et al. Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice. Proc. Natl Acad. Sci. USA 110, 16492–16497 (2013).

    Article
    ADS
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).

    Article
    CAS
    PubMed

    Google Scholar

  • Stringer, C. & Pachitariu, M. Cellpose3: one-click image restoration for improved cellular segmentation. Nat. Methods 22, 592–599 (2025).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Kelly, D. & Chowdhury, T. COIL-Edinburgh/ROI_NucleusColocalisation: nucleus colocalisation v2.01 (2.01). Zenodo https://doi.org/10.5281/zenodo.17200734 (2025).

  • Schopp, T. et al. The DUF3715 domain has a conserved role in RNA-directed transposon silencing. RNA 29, 1471–1480 (2023).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Rappsilber, J., Ishihama, Y. & Mann, M. Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal. Chem. 75, 663–670 (2003).

    Article
    ADS
    CAS
    PubMed

    Google Scholar

  • Chambers, M. C. et al. A cross-platform toolkit for mass spectrometry and proteomics. Nat. Biotechnol. 30, 918–920 (2012).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Mendes, M. L. et al. An integrated workflow for crosslinking mass spectrometry. Mol. Syst. Biol. 15, e8994 (2019).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).

    Article
    ADS
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Mirdita, M. et al. ColabFold: making protein folding accessible to all. Nat. Methods 19, 679–682 (2022).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Jurrus, E. et al. Improvements to the APBS biomolecular solvation software suite. Protein Sci. 27, 112–128 (2018).

    Article
    CAS
    PubMed

    Google Scholar

  • Yariv, B. et al. Using evolutionary data to make sense of macromolecules with a “face-lifted” ConSurf. Protein Sci. 32, e4582 (2023).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).

    Article
    PubMed
    PubMed Central

    Google Scholar

  • Waterhouse, A. M., Procter, J. B., Martin, D. M., Clamp, M. & Barton, G. J. Jalview Version 2 — a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189–1191 (2009).

    Article
    CAS
    PubMed
    PubMed Central

    Google Scholar

  • UniProt, C. UniProt: the Universal Protein Knowledgebase in 2025. Nucleic Acids Res. 53, D609–D617 (2025).

    Article

    Google Scholar

  • Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017).

    Article
    ADS
    PubMed
    PubMed Central

    Google Scholar

  • Chowdhury, T. tamchow/spocd1_pirna-directed-dna-met-variance: Version of record for manuscript submission (1.0). Zenodo https://doi.org/10.5281/zenodo.17162836 (2025).

  • Berrens, R. rberrens/SPOCD1-piRNA_directed_DNA_met: 20240114_release (v1.0.2). Zenodo https://doi.org/10.5281/zenodo.10509247 (2024).

  • Tyanova, S. et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Methods 13, 731–740 (2016).

    Article
    CAS
    PubMed

    Google Scholar



  • ■ مصدر الخبر الأصلي

    نشر لأول مرة على: www.nature.com

    تاريخ النشر: 2026-01-14 02:00:00

    الكاتب: Tamoghna Chowdhury

    تنويه من موقع “yalebnan.org”:

    تم جلب هذا المحتوى بشكل آلي من المصدر:
    www.nature.com
    بتاريخ: 2026-01-14 02:00:00.
    الآراء والمعلومات الواردة في هذا المقال لا تعبر بالضرورة عن رأي موقع “yalebnan.org”، والمسؤولية الكاملة تقع على عاتق المصدر الأصلي.

    ملاحظة: قد يتم استخدام الترجمة الآلية في بعض الأحيان لتوفير هذا المحتوى.

    اظهر المزيد

    مقالات ذات صلة

    زر الذهاب إلى الأعلى