Remembering foods and foes: emerging principles of transcriptional memory

Transcriptional memory is characterized by a primed cellular state, induced by an external stimulus that results in an altered expression of primed genes upon re-exposure to the inducing signal. Intriguingly, the primed state is heritably maintained across somatic cell divisions even after the initial stimulus and target gene transcription cease. This phenomenon is widely observed across various organisms and appears to enable cells to retain a memory of external signals, thereby adapting to environmental changes. Signals range from nutrient supplies (food) to a variety of stress signals, including exposure to pathogens (foes), leading to long-term memory such as in the case of trained immunity in plants and mammals. Here, we review these priming phenomena and our current understanding of transcriptional memory. We consider different mechanistic models for how memory can work and discuss existing evidence for potential carriers of memory. Key molecular signatures include: the poising of RNA polymerase II machinery, maintenance of histone marks, as well as alterations in nuclear positioning and long-range chromatin interactions. Finally, we discuss the potential adaptive roles of transcriptional memory in the organismal response to its environment from nutrient sensing to trained immunity.