An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability.

In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation 'chromatin switch' on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation.

Mapping the Morphological Landscape of Oligomeric Di-block Peptide-Polymer Amphiphiles.

Peptide-polymer amphiphiles (PPAs) are tunable hybrid materials that achieve complex assembly landscapes by combining the sequence-dependent properties of peptides with the structural diversity of polymers. Despite their promise as biomimetic materials, determining how polymer and peptide properties simultaneously affect PPA self-assembly remains challenging. We herein present a systematic study of PPA structure-assembly relationships. PPAs containing oligo(ethyl acrylate) and random-coil peptides were used to determine the role of oligomer molecular weight, dispersity, peptide length, and charge density on self-assembly. We observed that PPAs predominantly formed spheres rather than anisotropic particles. Oligomer molecular weight and peptide hydrophilicity dictated morphology, while dispersity and peptide charge affected particle size. These key benchmarks will facilitate the rational design of PPAs that expand the scope of biomimetic functionality within assembled soft materials.