SIRT7 regulates dosage compensation and safeguards the female X chromosome

Data availability

All new datasets generated from this work have been deposited in GEO under accession GSE256287 . The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository under dataset identifier PXD057198 .  Source data are provided with this paper.

Code availability

The custom code for RNA-seq and related ChIP–seq presented in this study is archived at Zenodo 96 ( https://doi.org/10.5281/zenodo.19464181 ).

References

Vaquero, A. The conserved role of sirtuins in chromatin regulation. Int. J. Dev. Biol. 53 , 303–322 (2009).

Article

CAS

PubMed

Google Scholar

Giblin, W., Skinner, M. E. & Lombard, D. B. Sirtuins: guardians of mammalian healthspan. Trends Genet. 30 , 271–286 (2014).

Article

CAS

PubMed Central

PubMed

Google Scholar

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).

Article

CAS

PubMed Central

PubMed

Google Scholar

Kim, H.-S. et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell 20 , 487–499 (2011).

Article

CAS

PubMed Central

PubMed

Google Scholar

Kanfi, Y. et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483 , 218–221 (2012).

Article

ADS

CAS

PubMed

Google Scholar

Peshti, V. et al. Characterization of physiological defects in adult SIRT6 −/− mice. PLoS ONE 12 , e0176371 (2017).

Article

PubMed Central

PubMed

Google Scholar

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).

Article

Google Scholar

Lyon, M. F. Gene action in the X-chromosome of the mouse ( Mus musculus L.). Nature 190 , 372–373 (1961).

Article

ADS

CAS

PubMed

Google Scholar

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).

Article

Google Scholar

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).

Article

CAS

PubMed Central

PubMed

Google Scholar

Bosch-Presegue, L. & Vaquero, A. Sirtuins in stress response: guardians of the genome. Oncogene 33 , 3764–3775 (2014).

Article

CAS

PubMed

Google Scholar

Martínez-Redondo, P. & Vaquero, A. The diversity of histone versus nonhistone sirtuin substrates. Genes Cancer 4 , 148–163 (2013).

Article

PubMed Central

PubMed

Google Scholar

Bheda, P., Jing, H., Wolberger, C. & Lin, H. The substrate specificity of sirtuins. Annu. Rev. Biochem. 85 , 405–429 (2016).

Article

CAS

PubMed

Google Scholar

Simonet, N. G. et al. SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1. Sci. Adv. 6 , eaaz2590 (2020).

Article

ADS

CAS

PubMed Central

PubMed

Google Scholar

Vazquez, B. N. et al. SIRT 7 promotes genome integrity and modulates non-homologous end joining DNA repair. EMBO J. 35 , 1488–1503 (2016).

Article

CAS

PubMed Central

PubMed

Google Scholar

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).

Article

CAS

PubMed Central

PubMed

Google Scholar

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).

Article

ADS

CAS

PubMed Central

PubMed

Google Scholar

Ford, E. et al. Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev.   20 , 1075–1080 (2006).

Article

CAS

PubMed Central

PubMed

Google Scholar

Blank, M. F. et al. SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II transcription. Nucleic Acids Res. 45 , 2675–2686 (2017).

Article

ADS

CAS

PubMed Central

PubMed

Google Scholar

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).

Article

CAS

Google Scholar

Barber, M. F. et al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature 487 , 114–118 (2012).

Article

ADS

CAS

PubMed Central

PubMed

Google Scholar

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).

Article

ADS

CAS

PubMed Central

PubMed

Google Scholar

Żylicz, J. J. et al. The implication of early chromatin changes in X chromosome inactivation. Cell…