Pharmacodynamics. Epigenetic changes can trigger a state change for the entire cell, for in-
stance, in the case in which DNA methylation regulates gene transcription. Methylation can
completely silence a gene, and demethylation can render it fully functional at the transcriptional
level. Thus, the effects of manipulating the methylome can be all-or-none. In classical pharma-
codynamics terms, these agents can exhibit extreme positive cooperation. Theoretically, a single
cytosine methylation event in a cell can completely silence the associated gene, one single molec-
ular modification triggering a state change for the cell’s transcriptional complement.
Moreover, there is an emerging literature suggesting possible transgenerational effects of al-
tered DNA methylation—not just teratogenic effects of drug exposure in utero, but possible her-
itable and self-perpetuating germline modifications that can be perpetuated across generations.
This represents an entirely different type of pharmacodynamics: a drug effect in the absence of
the organism ever having directly experienced the drug.