Table 1.
Crosstalk between NO and DNA methyltransferases, histone deacetylases, histone methyltransferases and histone demethylases. The table indicates the names of the enzyme involved and its substrate. It summarizes the connections between epigenetic regulators and NO and the impact in cancer.
| Epigenetic Regulation | Enzyme | Transcriptional Role | Crosstalk between NO and Epigenetic Regulators | Impact of the Regulatory Mechanism in Carcinogenesis | References |
|---|---|---|---|---|---|
| DNA methylation | DNMT not specified | Transcriptional repression | NOS-2-derived NO reduces tumor suppression genes expression | Pro-tumoral | [45] |
| DNMT not specified | Transcriptional repression | NO induces E-cadherin methylation by IL-1B decreasing E-cadherin expression | Pro-tumoral | [44] | |
| DNMT not specified | Ectopic expression | NO causes ectopic expression of AID and enhances NOS2 expression | Pro-tumoral | [46] | |
| Histone deacetylation | HDAC6 | Transcriptional repression | NO induces HDAC6 S-nitrosation | Pro-tumoral | [60] |
| HDAC2 | Transcriptional repression | NO S-nitrosation weakens HDAC2 enzymatic function | Anti-tumoral | [58] | |
| CBP | Transcriptional repression | CBP silencing decreases NO production by downregulation NOS-3 | Anti-tumoral | [61,62] | |
| SIRT1 | |||||
| Histone methylation | G9a | Transcriptional repression | NO downregulates expression | Anti-tumoral | [64,67,68] |
| SETDB2 | NO upregulates expression | Pro-tumoral | [64,69] | ||
| SUV39H2 | |||||
| SUV30H1 | NO indirectly targets SUV20H1 for proteasomal degradation | Anti-tumoral | [70,71,72] | ||
| MLL | Transcriptional activation | Not described | Pro-tumoral | [74] | |
| SET-1A | SET-1A trimethylates NOS2 promoter in response to IL-1 | Pro-tumoral | [75] | ||
| EZH2 | Transcriptional repression | EZH2 does not control NOS2 expression. Other mechanism should be involved | Pro-tumoral | [79,80] | |
| Histone demethylation | KDM3A | Transcriptional activation | NO inhibits KDM3A by forming a nitrosyl–iron complex | Anti-tumoral | [64,65,66] |
| KDM3B | NO upregulates expression. Compensatory mechanism in response to NO mediated KDM3A inhibition | Not described | [64] | ||
| KDM4A | |||||
| KDM4B | |||||
| KDM4C | |||||
| KDM4D | |||||
| KDM1 | |||||
| KDM7A | |||||
| KDMA | Transcriptional repression | Not described | Pro-tumoral | [76] | |
| KDMB | [77,78] | ||||
| KDM2A | Transcriptional repression | NO promotes the expression of Oct-4, which is related to reduced expression of demethylase KDM2A | Pro-tumoral | [81,82] |