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Review
. 2025 Aug;41(8):691-705.
doi: 10.1016/j.tig.2025.04.009. Epub 2025 May 15.

Epitranscriptome-epigenome interactions in development and disease mechanisms

Affiliations
Review

Epitranscriptome-epigenome interactions in development and disease mechanisms

Chengyu Li et al. Trends Genet. 2025 Aug.

Abstract

Crosstalk between epitranscriptomic modifications to RNA and epigenomic modifications to DNA and histones plays fundamental roles in development and disease. Here, we summarize two major regulatory modes of the crosstalk between the epigenome and epitranscriptome. In the 'cis mode', the crosstalk occurs co-transcriptionally, with direct interactions observed between epigenetic modifications mediated by their regulators. In the 'trans mode', the modification of an epigenetic layer regulates the expression of another epigenetic layer's writers/erasers and subsequently induces downstream epigenetic alteration. Additionally, we focus on the functional roles of the crosstalk mechanism in physiological and pathological contexts, including development, differentiation, cancer, and complex genetic diseases. Lastly, we discuss the potential future directions for a systematic understanding of epigenetic crosstalk in development and disease.

Keywords: RNA modification; epigenetic crosstalk; epigenome; gene regulation.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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