Vaquero, A. The conserved role of sirtuins in chromatin regulation. Int. J. Dev. Biol. 53, 303–322 (2009).
Giblin, W., Skinner, M. E. & Lombard, D. B. Sirtuins: guardians of mammalian healthspan. Trends Genet. 30, 271–286 (2014).
Kim, H.-S. et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 17, 41–52 (2010).
Kim, H.-S. et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell 20, 487–499 (2011).
Kanfi, Y. et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483, 218–221 (2012).
Peshti, V. et al. Characterization of physiological defects in adult SIRT6−/− mice. PLoS ONE 12, e0176371 (2017).
de Arellano, M. L. B. et al. Sex differences in the aging human heart: decreased sirtuins, pro-inflammatory shift and reduced anti-oxidative defense. Aging 11, 1918–1933 (2019).
Lyon, M. F. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190, 372–373 (1961).
Lessing, D., Anguera, M. C. & Lee, J. T. X chromosome inactivation and epigenetic responses to cellular reprogramming. Annu. Rev. Genom. Hum. Genet. 14, 85–110 (2012).
Wei, C., Kesner, B., Yin, H. & Lee, J. T. Imprinted X chromosome inactivation at the gamete-to-embryo transition. Mol. Cell 84, 1442–1459.e7 (2024).
Bosch-Presegue, L. & Vaquero, A. Sirtuins in stress response: guardians of the genome. Oncogene 33, 3764–3775 (2014).
Martínez-Redondo, P. & Vaquero, A. The diversity of histone versus nonhistone sirtuin substrates. Genes Cancer 4, 148–163 (2013).
Bheda, P., Jing, H., Wolberger, C. & Lin, H. The substrate specificity of sirtuins. Annu. Rev. Biochem. 85, 405–429 (2016).
Simonet, N. G. et al. SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1. Sci. Adv. 6, eaaz2590 (2020).
Vazquez, B. N. et al. SIRT 7 promotes genome integrity and modulates non-homologous end joining DNA repair. EMBO J. 35, 1488–1503 (2016).
Vazquez, B. N., Blengini, C. S., Hernandez, Y., Serrano, L. & Schindler, K. SIRT7 promotes chromosome synapsis during prophase I of female meiosis. Chromosoma 128, 369–383 (2019).
Sun, S. et al. Vascular endothelium-targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model. Sci. Adv. 6, eaay5556 (2020).
Ford, E. et al. Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev. 20, 1075–1080 (2006).
Blank, M. F. et al. SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II transcription. Nucleic Acids Res. 45, 2675–2686 (2017).
Tsai, Y.-C., Greco, T. M., Boonmee, A., Miteva, Y. & Cristea, I. M. Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Mol. Cell. Proteom. 11, 60–76 (2012).
Barber, M. F. et al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature 487, 114–118 (2012).
Wang, W. W. et al. A click chemistry approach reveals the chromatin-dependent histone H3K36 deacylase nature of SIRT7. J. Am. Chem. Soc. 141, 2462–2473 (2019).
Żylicz, J. J. et al. The implication of early chromatin changes in X chromosome inactivation. Cell 176, 182–197 (2019).
Nguyen, D. K. & Disteche, C. M. Dosage compensation of the active X chromosome in mammals. Nat. Genet. 38, 47–53 (2006).
Lin, H. et al. Dosage compensation in the mouse balances up-regulation and silencing of X-linked genes. PLoS Biol. 5, e326 (2007).
Larsson, A. J. M., Coucoravas, C., Sandberg, R. & Reinius, B. X-chromosome upregulation is driven by increased burst frequency. Nat. Struct. Mol. Biol. 26, 963–969 (2019).
Lentini, A. et al. Elastic dosage compensation by X-chromosome upregulation. Nat. Commun. 13, 1854 (2022).
Costanzi, C. & Pehrson, J. R. Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature 393, 599–601 (1998).
Plath, K. et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 300, 131–135 (2003).
Zhao, J., Sun, B. K., Erwin, J. A., Song, J.-J. & Lee, J. T. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322, 750–756 (2008).
Paredes, S. et al. The epigenetic regulator SIRT7 guards against mammalian cellular senescence induced by ribosomal DNA instability. J. Biol. Chem. 293, 11242–11250 (2018).
Zhang, L.-F., Huynh, K. D. & Lee, J. T. Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing. Cell 129, 693–706 (2007).
Vazquez, B. N. et al. SIRT7 and p53 interaction in embryonic development and tumorigenesis. Front. Cell Dev. Biol. 11, 1281730 (2024).
Vazquez, B. N. et al. SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina. Nucleic Acids Res. 47, 7870–7885 (2019).
Pinter, S. F. et al. Spreading of X chromosome inactivation via a hierarchy of defined Polycomb stations. Genome Res. 22, 1864–1876 (2012).
Monk, M. & Harper, M. I. Sequential X chromosome inactivation coupled with cellular differentiation in early mouse embryos. Nature 281, 311–313 (1979).
Colognori, D., Sunwoo, H., Wang, D., Wang, C.-Y. & Lee, J. T. Xist repeats A and B account for two distinct phases of X inactivation establishment. Dev. Cell https://doi.org/10.1016/j.devcel.2020.05.021 (2020).
Ogawa, Y., Sun, B. K. & Lee, J. T. Intersection of the RNA interference and X-inactivation pathways. Science 320, 1336–1341 (2008).
Bauer, M. et al. Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation. Nat. Commun. 12, 3499 (2021).
Morris, S. A. et al. Identification of histone H3 lysine 36 acetylation as a highly conserved histone modification. J. Biol. Chem. 282, 7632–7640 (2007).
McLean, C. Y. et al. GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495–501 (2010).
Vakhrusheva, O. et al. Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ. Res. 102, 703–710 (2008).
Ryu, D. et al. A SIRT7-dependent acetylation switch of GABPβ1 controls mitochondrial function. Cell Metab. 20, 856–869 (2014).
Fukuda, M. et al. SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix. Nat. Commun. 9, 2833 (2018).
Kaneko, S. et al. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev. 24, 2615–2620 (2010).
Rao, S. S. P. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014).
Giorgetti, L. et al. Structural organization of the inactive X chromosome in the mouse. Nature 535, 575–579 (2016).
Froberg, J. E., Pinter, S. F., Kriz, A. J., Jégu, T. & Lee, J. T. Megadomains and superloops form dynamically but are dispensable for X-chromosome inactivation and gene escape. Nat. Commun. 9, 5004 (2018).
Wang, C.-Y., Jégu, T., Chu, H.-P., Oh, H. J. & Lee, J. T. SMCHD1 merges chromosome compartments and assists formation of super-structures on the inactive X. Cell 174, 406–421 (2018).
Cheutin, T. & Cavalli, G. Polycomb silencing: from linear chromatin domains to 3D chromosome folding. Curr. Opin. Genet. Dev. 25, 30–37 (2014).
Pai, C.-C. et al. A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice. Nat. Commun. 5, 4091 (2014).
Kim, H., Jo, H., Seo, H. D., Park, H.-S. & Lee, D. Chd1p recognizes H3K36Ac to maintain nucleosome positioning near the transcription start site. Biochem. Biophys. Res. Commun. 503, 1200–1206 (2018).
Deng, X. et al. Bipartite structure of the inactive mouse X chromosome. Genome Biol. 16, 152 (2015).
Crane, E. et al. Condensin-driven remodelling of X chromosome topology during dosage compensation. Nature 523, 240–244 (2015).
Serra, F. et al. Automatic analysis and 3D-modelling of Hi-C data using TADbit reveals structural features of the fly chromatin colors. PLoS Comput. Biol. 13, e1005665 (2017).
Lappala, A. et al. Four-dimensional chromosome reconstruction elucidates the spatiotemporal reorganization of the mammalian X chromosome. Proc Natl Acad. Sci. USA 118, e2107092118 (2021).
Stewart, N. & Bacchetti, S. Expression of SV40 large T antigen, but not small t antigen, is required for the induction of chromosomal aberrations in transformed human cells. Virology 180, 49–57 (1991).
Mah, L.-J., El-Osta, A. & Karagiannis, T. C. γH2AX: a sensitive molecular marker of DNA damage and repair. Leukemia 24, 679–686 (2010).
Löbrich, M., Rydberg, B. & Cooper, P. K. Repair of x-ray-induced DNA double-strand breaks in specific Not I restriction fragments in human fibroblasts: joining of correct and incorrect ends. Proc. Natl Acad. Sci. USA 92, 12050–12054 (1995).
Leem, J., Kim, J.-S. & Oh, J. S. Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A–MDC1–TOPBP1 complex from spindle pole to chromosomes. Nucleic Acids Res. 51, 4899–4913 (2023).
Baudat, F., Imai, Y. & de Massy, B. Meiotic recombination in mammals: localization and regulation. Nat. Rev. Genet. 14, 794–806 (2013).
Yuan, L. et al. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol. Cell 5, 73–83 (2000).
Fukuda, T., Daniel, K., Wojtasz, L., Toth, A. & Höög, C. A novel mammalian HORMA domain-containing protein, HORMAD1, preferentially associates with unsynapsed meiotic chromosomes. Exp. Cell. Res. 316, 158–171 (2010).
Mahadevaiah, S. K. et al. Recombinational DNA double-strand breaks in mice precede synapsis. Nat. Genet. 27, 271–276 (2001).
Guitart-Solanes, A. et al. SIRT7 links H3K36ac epigenetic regulation with genome maintenance in the mouse testis. Nat. Commun. https://doi.org/10.1038/s41467-026-72540-3 (2025).
Disteche, C. M. Dosage compensation of the sex chromosomes and autosomes. Semin. Cell Dev. Biol. 56, 9–18 (2016).
Deng, X. et al. Mammalian X upregulation is associated with enhanced transcription initiation, RNA Half-Life, and MOF-Mediated H4K16 acetylation. Dev. Cell 25, 55–68 (2013).
Deng, X. & Disteche, C. M. Rapid transcriptional bursts upregulate the X chromosome. Nat. Struct. Mol. Biol. 26, 851–853 (2019).
Deng, X., Berletch, J. B., Nguyen, D. K. & Disteche, C. M. X chromosome regulation: diverse patterns in development, tissues and disease. Nat. Rev. Genet. 15, 367–378 (2014).
Jégu, T., Aeby, E. & Lee, J. T. The X chromosome in space. Nat. Rev. Genet. 18, 377–389 (2017).
Balaton, B. P., Dixon-McDougall, T., Peeters, S. B. & Brown, C. J. The eXceptional nature of the X chromosome. Hum. Mol. Genet. 27, R242–R249 (2018).
Fang, H., Deng, X. & Disteche, C. M. X-factors in human disease: impact of gene content and dosage regulation. Hum. Mol. Genet. 30, R285–R295 (2021).
Yildirim, E., Sadreyev, R. I., Pinter, S. F. & Lee, J. T. X-chromosome hyperactivation in mammals via nonlinear relationships between chromatin states and transcription. Nat. Struct. Mol. Biol. 19, 56–61 (2011).
Yuan, W. et al. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J. Biol. Chem. 286, 7983–7989 (2011).
Cai, L. et al. An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. Mol. Cell 49, 571–582 (2013).
Yu, J. et al. Regulation of serine-threonine kinase Akt activation by NAD+-dependent deacetylase SIRT7. Cell Rep. 18, 1229–1240 (2017).
Yoshida, M., Horinouchi, S. & Beppu, T. Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. BioEssays 17, 423–430 (1995).
Ekwall, K., Olsson, T., Turner, B. M., Cranston, G. & Allshire, R. C. Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 91, 1021–1032 (1997).
Cimini, D., Mattiuzzo, M., Torosantucci, L. & Degrassi, F. Histone hyperacetylation in mitosis prevents sister chromatid separation and produces chromosome segregation defects. Mol. Biol. Cell 14, 3821–3833 (2003).
Mulla, W. A. et al. Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast. eLife 6, e27991 (2017).
Stalpers, L. J. A. & Kaplan, E. L. Edward L. Kaplan and the Kaplan–Meier survival curve. BSHM Bull. J. Br. Soc. Hist. Math. 33, 109–135 (2018).
Minajigi, A. et al. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science 349, aab2276 (2015).
Durand, N. C. et al. Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments. Cell Syst. 3, 95–98 (2016).
Plimpton, S. Fast parallel algorithms for short-range molecular dynamics. J. Comput. Phys. 117, 1–19 (1995).
Liebe, B., Alsheimer, M., Höög, C., Benavente, R. & Scherthan, H. Telomere attachment, meiotic chromosome condensation, pairing, and bouquet stage duration are modified in spermatocytes lacking axial elements. Mol. Biol. Cell 15, 827–837 (2004).
Hamada, N. et al. Germ cell-intrinsic effects of sex chromosomes on early oocyte differentiation in mice. PLoS Genet. 16, e1008676 (2020).
Rosario, B. C. D. et al. Genetic intersection of Tsix and Hedgehog signaling during the initiation of X-chromosome inactivation. Dev. Cell 43, 359–371 (2017).
Tarasov, A., Vilella, A. J., Cuppen, E., Nijman, I. J. & Prins, P. Sambamba: fast processing of NGS alignment formats. Bioinformatics 31, 2032–2034 (2015).
Simon, M. D. et al. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature https://doi.org/10.1038/nature12719 (2013).
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010).
Wingett, S. W. & Andrews, S. FastQ Screen: a tool for multi-genome mapping and quality control. F1000Res. 7, 1338 (2018).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Dignam, J. D., Lebovitz, R. M. & Roeder, R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11, 1475–1489 (1983).
Simonet, N. G. Code for ‘SIRT7 regulates dosage compensation and safeguards the female X-chromosome’. Zenodo https://doi.org/10.5281/zenodo.19464181 (2026).