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DNMT3A binds ubiquitinated histones to regulate bivalent genes

A new study demonstrates that the disordered N-terminal domain of DNMT3A1 binds PRC1-catalyzed H2AK119ub, targeting DNA methylation to bivalent promoters in mouse brain cortical cells. Methylation around bivalent genes is critical for mouse postnatal development, and could be equally important in other cell types and in disease.

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Fig. 1: DNMT3A1 has a disordered N-terminal domain, missing from the other isoform DNMT3A2, that binds ubiquitinated lysine 119 on histone H2A (H2AK119ub).


  1. Li, E. & Zhang, Y. Cold Spring Harb. Perspect. Biol. 6, a019133 (2014).

    Article  Google Scholar 

  2. Okano, M., Bell, D. W., Haber, D. A. & Li, E. Cell 99, 247–257 (1999).

    CAS  Article  Google Scholar 

  3. Remacha, L. et al. Genet. Med. Off. J. Am. Coll. Med. Genet. 20, 1644–1651 (2018).

    CAS  Google Scholar 

  4. Heyn, P. et al. Nat. Genet. 51, 96–105 (2019).

    CAS  Article  Google Scholar 

  5. Yang, L., Rau, R. & Goodell, M. A. Nat. Rev. Cancer 15, 152–165 (2015).

    CAS  Article  Google Scholar 

  6. Otani, J. et al. EMBO Rep. 10, 1235–1241 (2009).

    CAS  Article  Google Scholar 

  7. Dhayalan, A. et al. J. Biol. Chem. 285, 26114–26120 (2010).

    CAS  Article  Google Scholar 

  8. Gu, T. et al. Nat. Genet. (2022).

    Article  PubMed  Google Scholar 

  9. Bernstein, B. E. et al. Cell 125, 315–326 (2006).

    CAS  Article  Google Scholar 

  10. Azuara, V. et al. Nat. Cell Biol. 8, 532–538 (2006).

    CAS  Article  Google Scholar 

  11. Johnson, K. C. et al. Nat. Commun. 7, 13177 (2016).

    CAS  Article  Google Scholar 

  12. Verma, N. et al. Nat. Genet. 50, 83–95 (2018).

    CAS  Article  Google Scholar 

  13. Bachman, M. et al. Nat. Chem. 6, 1049–1055 (2014).

    CAS  Article  Google Scholar 

  14. Reddington, J. P. et al. Genome Biol. 14, R25 (2013).

    Article  Google Scholar 

  15. Weinberg, D. N. et al. Nat. Genet. 53, 794–800 (2021).

    CAS  Article  Google Scholar 

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Correspondence to Aled J. Parry.

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W.R. is a consultant and shareholder of Cambridge Epigenetix. W.R. is employed by Altos Labs. The remaining authors declare no competing interests.

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Parry, A.J., Reik, W. DNMT3A binds ubiquitinated histones to regulate bivalent genes. Nat Genet 54, 537–538 (2022).

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