## Results
### Transcription Factors Likely to Be recruited by m6A  
In order to identify transcription factors (TFs) that are likely recruited by m6A, we referred to \"ENCODE and ChEA Consensus TFs from ChIP-X\" category in Enrichr (full list is available as Supplementary Materials). This category is the consensus list between two independent research projects, ENCODE [22] and ChEA [23], where TF binding to human genome was comprehensively investigated by ChIP-Seq experiments.  
There were 27 TFs commonly selected (Figure 5 and Table 5), which also suggests the success of TD-based unsupervised FE, since it is unlikely that there are significant overlaps between TFs selected using two independent datasets. Some of these TFs are reported to be related to open chromatin. AR [24] is related to chromatin accessibility. E2F1 is also reported to be associated with regulating chromatin components [25]. ESR1 [26] mediates allele-specific chromatin recruitment. GATA2 [27] mediates looped chromatin organization. KLF4 is involved in the organization and regulation of enhancer networks [28]. MYC drives chromatin accessibility [29]. NANOG establishes chromatin accessibility [30]. PPAR\(\gamma\) binding induces open chromatin and histone acetylation (Figure 7 [31]). The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells is observed [32]. SALL4 promotes glycolysis and chromatin remodeling [33]. STAT3 plays some roles in regulator of chromatin topology [34]. TP53 engages distinct local chromatin environments [35]. TP63 cooperates with CTCF to modulate chromatin architecture [36]. CHD1 regulates open chromatin [37]. RCOR1 is known as a chromatin regulator [38]. TAF1 has some relationship with histone acetyltransferases [39]. UBTF1 and UBTF2 bind to open chromatin structures [40]. YY1 was listed as one that promotes open chromatin and activates transcription [13]. ZBTB7A is a transducer for the control of promoter accessibility [41]. This also suggests that TD-based unsupervised FE identifies the potential TFs that regulate chromatin structure as expected.  
Figure 5: Venn diagram of TFs in ”ENCODE and ChEA Consensus TFs from ChIP-X” category, selected by uploading genes selected by TD-based unsupervised FE to Enrichr.  
In addition to such literature as mentioned above, we also tried to identify interactions between TFs and enrichment analysis of TFs themselves.  
Not only are they tightly interrelated, but also the four representative TFs, MYC, STAT3, SMAD4, and TP53, regulate most of these TFs. This strongly suggests that TD-based unsupervised FE successfully identified genes that are important parts of the regulatory network.  
It is also interesting to see what kind of biological processes are controlled by the TF network shown in Figure 6. In order to see this, we uploaded 27 TFs to REACTOME [42] (Table 6).  
First of all, there are many transcription regulation-related pathways that are enriched in candidate TFs that m6A recruits. Second, there are many descriptions that suggest the relationship with chromatin reorganizations (see Supplementary Materials). For example, TFs that belong to \"Generic Transcription Pathway\" are known to act as co-activator and co-repressor complexes that affect histone modifications. TFs that belong to \"Gene expression\" are known to cause epigenetic changes that result in altered chromatin complexes that influence transcription. TFs that belong to \"Estrogen-dependent gene expression\" are known to establish active chromatin marks. Thus, from the points of functions also, these TFs are very suitable to be recruited by m6A.  
Figure 6: The networks between 27 TFs are listed in Table 5 retrieved from TRRUST2 [43]. Full information is available as Supplementary Material.  
\begin{table}
\begin{tabular}{c c} \hline \hline CHEA & AR E2F1 ESR1 GATA2 KLF4 MYC NANOG NFE2L2 PPARG POU5F1 SMAD4 SALL4 SOX2 STAT3 TP53 TP63 ENCODE & CHD1 CTCF PBX3 RCOR1 RELA TAF1 TCF3 UBTF YY1 ZBTB7A ZNF384 \\ \hline \hline \end{tabular}
\end{table}
Table 5: Twenty seven commonly selected TFs from Figure 5.