title: A dynamic model of transcriptional imprinting derived from the vitellogenesis memory effect.
abstract: Transcriptional memory of transient signals can be imprinted on living systems and influence their reactivity to repeated stimulations. Although they are classically ascribed to structural chromatin rearrangements in eukaryotes, such behaviors can also rely on dynamic memory circuits with sustained self-amplification loops. However, these phenomena are either of finite duration, or conversely associated to sustained phenotypic changes. A mechanism is proposed, in which only the responsiveness of the target gene is durably reset at a higher level after primary stimulation, using the celebrated but still puzzling vitellogenesis memory effect. The basic ingredients of this system are: 1), a positive autoregulation of the estrogen receptor α gene; 2), a strongly cooperative action of the estradiol receptor on vitellogenin expression; and 3), a variant isoform of the estradiol receptor with two autonomous transcription-activating modules, one of which is signal-independent and the other, signal-dependent. Realistic quantification supports the possibility of a multistationary situation in which ligand-independent activity is unable by itself to prime the amplification loop, but can click the system over a memory threshold after a primary stimulation. This ratchet transcriptional mechanism can have developmental and ecotoxicological importance and explain lifelong imprinting of past exposures without apparent phenotypic changes before restimulation and without need for persistent chromatin modifications.
authors.affiliation: UMR6026 Interactions Cellulaires et Moléculaires IFR140 GFAS Irset, Université de Rennes1, Rennes, France.
authors.forename: Floriane
authors.initials: F
authors.lastname: Nicol-Benoit
authors.forename: Axelle
authors.initials: A
authors.lastname: Amon
authors.forename: Colette
authors.initials: C
authors.lastname: Vaillant
authors.forename: Pascale
authors.initials: P
authors.lastname: le Goff
authors.forename: Yves
authors.initials: Y
authors.lastname: le Dréan
authors.forename: Farzad
authors.initials: F
authors.lastname: Pakdel
authors.forename: Gilles
authors.initials: G
authors.lastname: Flouriot
authors.forename: Yves
authors.initials: Y
authors.lastname: Valotaire
authors.forename: Denis
authors.initials: D
authors.lastname: Michel
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D014818:Vitellogenesis / Q000235:genetics*; D014819:Vitellogenins / Q000235:genetics
chemical_list: D011960:Receptors, Estrogen; D014819:Vitellogenins