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Comment
. 2022 May;54(5):537-538.
doi: 10.1038/s41588-022-01073-4.

DNMT3A binds ubiquitinated histones to regulate bivalent genes

Aled J Parry  1 , Wolf Reik  2   3
Affiliations
Comment

DNMT3A binds ubiquitinated histones to regulate bivalent genes

Aled J Parry et al. Nat Genet. 2022 May.

Abstract

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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Figures

Fig. 1
Fig. 1
DNMT3A1 has a disordered N-terminal domain, missing from the other isoform DNMT3A2, that binds ubiquitinated lysine 119 on histone H2A (H2AK119ub). This binding directs DNMT3A1 to bivalent domains (H3K4me3+/H3K27me3+) in some contexts such as in neurons or where the PWWP domain is mutated.
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