S-Adenosyl methionine (SAM), the principal methyl donor for methylation reactions. By maintaining a sufficient SAM pool, compounds such as folic acid, methylcobalamin, betaine, and choline ensure that SMYD4 has the necessary substrates for its enzymatic action. These compounds participate in the one-carbon metabolism and methylation cycles, indirectly bolstering SMYD4's methyltransferase function.
The chromatin state is another determinant of SMYD4 activity. Chemicals like Suberoylanilide Hydroxamic Acid, a histone deacetylase inhibitor, and 5-Aza-2'-deoxycytidine, a DNA methyltransferase inhibitor, promote a more relaxed chromatin configuration. This alteration in chromatin structure can potentially enhance the access of SMYD4 to its histone targets, thus facilitating the methylation process. Additionally, nicotinamide, resveratrol, genistein, curcumin, and epigallocatechin gallate, interact with cellular signaling pathways and can modulate the activity of various proteins involved in epigenetic regulation. These interactions, while not directly influencing SMYD4, can lead to changes in the cellular environment that support the protein's role in chromatin modification.
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