Histone 4 lysine 5/12 acetylation provides a plasticity code with epigenetic memory of environmental exposure

Development can be altered to match phenotypes with the environment, and the genetic mechanisms that direct such alternative phenotypes are beginning to be elucidated[1][1],[2][2]. Yet, the rules that govern environmental sensitivity vs . invariant development (canalization), and potential epigenetic memory, remain unknown. Here, we show that plasticity of nematode mouth forms is determined by histone 4 lysine 5 and 12 acetylation (H4K5/12ac). Acetylation in early larval stages provides a permissive chromatin state at specific switch genes, which is susceptible to induction during the critical window of environmental sensitivity. As development proceeds deacetylation shuts off switch gene expression to end the critical period. We show that inhibiting deacetylase enzymes leads to long-term epigenetic memory, demonstrating that histone modifications in juveniles can carry environmental information to affect organismal traits in adults. This epigenetic regulation of plasticity appears to be derived from an ancient mechanism of licensing developmental speed that is conserved between flies and nematodes. Thus, H4K5/12ac provides a histone ‘plasticity’ code with epigenetic potential that can be stored and erased by acetylation and deacetylation, respectively. Highlights 1. Reciprocal transplant experiments reveal a critical time window of mouth-form plasticity. 2. Entry and exit of the critical window is determined by H4K5/12ac at the switch gene eud-1 . 3. H4K12ac maintains transcriptional competence by supporting elongation. 4. Inhibition of deacetylation freezes an initial developmental trajectory, resulting in long-term epigenetic memory. 5. H4K5/12 acetylation control of plasticity was co-opted from an ancestral role in controlling developmental speed. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-1 [2]: #ref-2