Table 1.
The complicated interactions between m6A and other epigenetic modifications
| Categories of epigenetics | Related components | m6A regulators | Mechanisms | References |
|---|---|---|---|---|
| DNA methylation | SlDML2 | SlALKBH2 | SlDML2-induced DNA methylation regulates the m6A demethylase SlALKBH2, while SlALKBH2-guided m6A demethylation strengthens the stability of 5mC demethylase SlDML2 in turn. | 62 |
| DNMT1, DNMT3a | METTL3 | The binding of DNMT1 and DNMT3a to METTL3 promoter is reduced by cigarette smoke condensate (CSC), leading to the hypomethylation of METTL3 and facilitating its expression. | 64 | |
| / | ALKBH5 | The CpG island of ALKBH5 is hypomethylated by CSC, which increases ALKBH5 expression. | 65 | |
| Chromatin remodeling | BAF155 | RBM15 | RBM15 accelerates the decay of chromatin remodeling factor BAF155 via the m6A methylation machinery. | 67 |
| carRNAs | METTL3 YTHDC1 |
METTL3 promotes m6A methylation of chromosome-associated regulatory RNAs (carRNAs), while YTHDC1 mediates their degradation. | 22 | |
| Histone modification | H3K27ac, H3K27me3, CBP, p300 | METTL14 | METTL14 not only alters H3K27me3 modification, but also regulates H3K27ac modification by destabilizing CBP and p300 mRNAs. | 21 |
| H3K27me3, Ezh2 | METTL3 | METTL3 deposits m6A modification on histone methyltransferase Ezh2, which increases the level of H3K27me3. | 70 | |
| H3K4me3 | METTL3, METTL14, WTAP | The m6A modification catalyzed by METTL3/METTL14/WTAP complex substantially strengthens H3K4me3 modification. | 71 | |
| JMJD6 | hnRNPA2B1 | Arginine demethylase JMJD6 activates hnRNPA2B1 through facilitating its demethylation at Arg226. | 72 | |
| H3K27ac | METTL3 | H3K27ac modification on the promoter of METTL3 triggers its transcription. | 73 | |
| H3K4me3, KDM5C | METTL14 | KDM5C-mediated demethylation of H3K4me3 suppresses METTL14 transcription. | 74 | |
| H3K36me3 | METTL14 | H3K36me3 mark recognized by METTL14 promotes the binding of m6A methyltransferase complex to adjacent RNA polymerase II, depositing m6A co-transcriptionally. | 75 | |
| H3K9me2, KDM3B | YTHDC1 | YTHDC1 induces the H3K9me2 demethylation via recruiting KDM3B to the m6A-marked chromatin regions. | 76 | |
| RNA modification | m1A | FTO | FTO mediates demethylation of m1A in tRNA. | 37 |
| YTHDF1-3, YTHDC1 | m6A-binding proteins YTHDF1-3 and YTHDC1 are capable of directly binding to the m1A sites. | 80 | ||
| YTHDF2 | YTHDF2 recognizes m1A-modified transcripts and mediates their decay. | 81 | ||
| m5C | YTHDF2 | m6A reader YTHDF2 and m5C writer NSUN2 cooperatively facilitate murine leukemia virus (MLV) replication. | 88 | |
| METTL3, METTL14 | METTL3/METTL14-mediated m6A methylation and NSUN2-mediated m5C methylation collaborate with each other to strengthen the expression of p21 mRNA. | 89 | ||
| YTHDF2 | YTHDF2 binds to m5C in rRNA with the Trp432 residue, remarkably decreasing the m5C level. | 90 | ||
| A-to-I | / | Loss of m6A modification contributes to the elevated level of A-to-I editing via the favorable association of ADAR with m6A-depleted transcripts. | 4 | |
| Pseudogene | METTL3 | METTL3 elevates the expression of lncRNA pseudogene Olfr29-ps1 and facilitates its sponge to miR-214-3p. | 94 | |
| / | m6A modification and pseudouridine (Ψ) collaboratively weaken the binding of RBP hPUM2 to its targeted RNAs. | 95 | ||
| m6Am | METTL3, WTAP, ALKBH5 | The m6Am signal can be detected in METTL3, WTAP and ALKBH5, while the m6A signal is found in m6Am writer PCIF1. | 105 | |
| FTO | FTO is responsible for the demethylation of both m6A and m6Am modifications. | 25, 37 |