The epitranscriptome, also known as RNA epigenetics, refers to the collection of chemical modifications on RNA molecules that regulate their function without altering the underlying nucleotide sequence [1]. These modifications, controlled by specific effector proteins, methyltransferases (writers), demethylases (erasers), and binding proteins (readers), are essential for modulating RNA metabolism and cellular processes in a dynamic and reversible manner. To date, over 170 modified ribonucleotides and the enzymes responsible for these modifications have been identified, emphasizing the critical role of epitranscriptomics in cellular function and human health [2]. Among these modifications, N6-methyladenosine (m6A) is the most prevalent in mRNA and plays a crucial role in regulating RNA metabolism, including RNA splicing, stability, and translation 3, 4. Importantly, recent studies have shown that m6A modification occurs on chromatin-associated regulatory RNA (carRNA), nascent RNA, repeats RNA, and centromeric RNA (cenRNA), significantly impact the interaction between RNA and chromatin 5, 6, 7, 8••. This modification modulates the recruitment of RNA-binding proteins and chromatin modifiers, thereby orchestrating transcriptional programs and chromatin architecture, facilitating context-dependent gene regulation. Such RNA–chromatin cross-talk is vital for maintaining cellular identity and adapting to developmental signals, further underscoring the importance of m6A modification in cellular regulation.

Utilizing gene knockout mouse models, researches have revealed that m6A modification is indispensable for early embryonic development, with its deficiency leading to abnormal gametogenesis and defects during both pre- and post-implantation stages 9, 10, 11. This modification is essential for regulating the maternal–zygotic transition, fate decisions, and lineage differentiation. With recent advancements in low cell input and single-cell m6A sequencing technologies, we now have the tools to reveal the m6A landscape across the entire transcriptome of reproductive cells 12••, 13•, 14, 15•. These technologies provide new insights into the dynamic changes and complex regulatory networks governed by m6A modification, particularly in rare samples and early embryonic development, enhancing our understanding of how m6A influences gene expression and developmental processes by regulating RNA metabolism.

In this review, we summarized recent advances in understanding the dynamic biological effects of m6A in transcriptional regulation during stem cells and early embryonic development, highlighting the significance of the interplay between m6A modification and chromatin regulation, as well as key issues that remain to be investigated in the future.