Mark Ptashne on the “incoherent and counterfactual world” of epigenetics

Ptashne again cuts through epic epigenetic confusion of transcription factors versus histone marks, cause versus effect.

“The Chemistry of Regulation of Genes and Other Things”:

As I have described, where the activated gene encodes the activator itself, we have memory: a self-perpetuating state of gene expression transmitted by regulatory proteins distributed to daughter cells as cells divide.

These now obvious ideas seem to be hard to accept for some. Ignoring the specificity problem and in the search for some alternative solution to the memory problem, they have created an incoherent and counterfactual world, one in which chromatin structure determines the activity of transcription factors (recruiters) rather than the other way around. Chromatin structure is usually meant to imply histone modifications, which somehow have acquired the name epigenetic modifications. The literature is replete with studies of histone modifications presented as studies of “epigenetics,”…

I find that discussing this matter is not entirely straightforward because sometimes it is hard to be sure what authors mean to say. Consider this recent example from a “Perspectives” article (published in the journal Science) that provides an overview of findings described in a research article in the same issue: “DNA variants influence a layer of gene regulation called epigenetics through the sequence-specific activity of transcription factors” (102). What, one wonders, do these authors mean by “a layer of gene regulation called epigenetics?” I think they mean “histone modifications,” but why use the word epigenetics? What do they mean by “influence,” and what would happen absent this influence?

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