2016/01/25 by Carolin C. Lechner, Ninad Agashe, Beat Fierz · 2 citations
Biochemistry, Genetics and Molecular Biology · #Cancer-related gene regulation #Epigenetics and DNA Methylation #Genomics and Chromatin Dynamics
paper · doi:10.1002/anie.201510996
openalex publication_date 2016/01/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
Nucleosomes carry extensive post-translational modifications (PTMs), which results in complex modification patterns that are involved in epigenetic signaling. Although two copies of each histone coexist in a nucleosome, they may not carry the same PTMs and are often differently modified (asymmetric). In bivalent domains, a chromatin signature prevalent in embryonic stem cells (ESCs), namely H3 methylated at lysine 4 (H3K4me3), coexists with H3K27me3 in asymmetric nucleosomes. We report a general, modular, and traceless method for producing asymmetrically modified nucleosomes. We further show that in bivalent nucleosomes, H3K4me3 inhibits the activity of the H3K27-specific lysine methyltransferase (KMT) polycomb repressive complex 2 (PRC2) solely on the same histone tail, whereas H3K27me3 stimulates PRC2 activity across tails, thereby partially overriding the H3K4me3-mediated repressive effect. To maintain bivalent domains in ESCs, PRC2 activity must thus be locally restricted or reversed.