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  • Histone 4 lysine 5/12 acetylation enables developmental plasticity of Pristionchus mouth form.

Histone 4 lysine 5/12 acetylation enables developmental plasticity of Pristionchus mouth form.

Nature communications (2023-04-14)
Michael S Werner, Tobias Loschko, Thomas King, Shelley Reich, Tobias Theska, Mirita Franz-Wachtel, Boris Macek, Ralf J Sommer
ABSTRACT

Development can be altered to match phenotypes with the environment, and the genetic mechanisms that direct such alternative phenotypes are beginning to be elucidated. Yet, the rules that govern environmental sensitivity vs. invariant development, 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, 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. Inhibiting deacetylase enzymes leads to fixation of prior developmental trajectories, demonstrating that histone modifications in juveniles can carry environmental information to adults. Finally, we provide evidence that this regulation was derived from an ancient mechanism of licensing developmental speed. Altogether, our results show that H4K5/12ac enables epigenetic regulation of developmental plasticity that can be stored and erased by acetylation and deacetylation, respectively.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
BIX 01294 trihydrochloride hydrate, ≥98% (HPLC), powder
Sigma-Aldrich
Histone Acetyltransferase p300 Inhibitor, C646, Histone Acetyltransferase p300 Inhibitor, C646, CAS 328968-36-1, is a cell-permeable, reversible inhibitor of p300/CBP HAT (Ki = 400 nM). Competes with acetyl-CoA for the p300 Lys-CoA binding pocket.
Sigma-Aldrich
Pyroxamide, ≥97% (HPLC)
Sigma-Aldrich
Anti-acetyl-Histone H4 (Lys12) Antibody, Trial Size, rabbit monoclonal, culture supernatant, Chemicon®
Sigma-Aldrich
GSK343, ≥98% (HPLC)
Sigma-Aldrich
Sodium butyrate, ≥98.5% (GC)
Sigma-Aldrich
SAHA, ≥98% (HPLC)
Sigma-Aldrich
CI−994, ≥98% (HPLC), powder
Sigma-Aldrich
Apicidin, ≥98% (HPLC), from microbial