29 m⁶A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation – 102 Transcriptomic Dataset Analyses

Figure 15

Hyperhomocysteinemia, folate cycle-related enzymes, m⁶A-RNA methylation regulators (m⁶A-RMRs), H3K4 methylases, and DNA methyltransferase regulate the expression of m⁶A-RMRs, suggesting a methylation hierarchy. (a) Hyperhomocysteinemia regulated fewer numbers of m⁶A-RMRs but more m⁶A-RMRs were changed after antihyperhomocysteinemia treatment in hyperhomocysteinemia animal model- (Rattus norvegicus) related microarray (GSE30308). The deficiencies of the folate cycle and metabolism related enzymes and m⁶A-RMRs affect the expression of m⁶A-RMRs. IGF2BP3 was upregulated with fold changes of 4.486, and FMR1 was downregulated with fold changes of 0.327 in the deficiency of methylenetetrahydrofolate Mthfd1. In the deficiencies of m⁶A-RMRs, writer RBM15 and WTAP were downregulated, and CBLL1 and YTHDF1 were upregulated. WTAP, HNRNPA2B1, IGF2BP2, ELAVL1, and RBMX were upregulated in the deficiency of FTO in thoracic aortae. (b) In mammals, SET1a and SET1b and MLL1–MLL4 are the main six enzymes that catalyze strimethylation of lysine 4 in histone H3 (H3K4). The deficiencies of MLL1, MLL2, and MLL4 can regulate the expression change of m⁶A-RMRs; regulation of m⁶A-RMRs by MLL1 is different in a circadian study (GSE24964); upregulated m⁶A-RMRs were increased in 30 hours compared to 18 hours in deficiency of MLL1; regulation of m⁶A-RMRs by the heterozygote of MLL2 is similar to the deficiency of homozygous (GSE67388); deficiency of homozygous MLL4 only regulates one of the 29 m⁶A-RMRs compared with heterozygous MLL4 (GSE30971). (c) In deficiency of DNA methyltransferases microarrays, the number of downregulated m⁶A-RMRs is more than that of upregulated m⁶A-RMRs. That is, maybe, DNA methyltransferases positively regulate m⁶A methylation. More differentially expressed m⁶A-RMRs in microarrays with deficiencies of DNMT1 are more than those in microarrays with DNMT3A or DNMT3B. Most m⁶A-RMRs (18/26) are differentially expressed, and the downregulated genes () are more than the upregulated genes () in DNMT1 knockdown myeloma cells (GSE86147).

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