A Modular Ligation Strategy for Asymmetric Bivalent Nucleosomes Trimethylated at K36 and K27

In nature, individual histones in the same nucleosome can carry identical (symmetric) or different (asymmetric) post‐translational modification (PTM) patterns, increasing the combinatorial complexity. Embryonic stem cells exhibit “bivalent” nucleosomes, some of which are marked by an asymmetric arra...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2019-05, Vol.20 (9), p.1124-1128
Main Authors: Guidotti, Nora, Lechner, Carolin C., Bachmann, Andreas L., Fierz, Beat
Format: Article
Language:English
Subjects:
asymmetric nucleosomes
Asymmetry
bivalent domains
Chromatin
Combinatorial analysis
Disulfides - chemical synthesis
Disulfides - chemistry
Embryo cells
Embryos
epigenetics
expressed protein ligation
Histones
Histones - chemical synthesis
Histones - chemistry
Histones - metabolism
Humans
Lysine - chemistry
Methylation
Methyltransferase
Nucleosomes
Nucleosomes - chemistry
Nucleosomes - metabolism
Polycomb Repressive Complex 2 - chemistry
Polycomb Repressive Complex 2 - metabolism
Protein Binding
protein modifications
Stem cells
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Summary:In nature, individual histones in the same nucleosome can carry identical (symmetric) or different (asymmetric) post‐translational modification (PTM) patterns, increasing the combinatorial complexity. Embryonic stem cells exhibit “bivalent” nucleosomes, some of which are marked by an asymmetric arrangement of H3K36me3 (an activating PTM) and H3K27me3 (a repressive PTM). Here we describe a modular synthetic method to access such asymmetrically modified nucleosomes and show that H3K36me3 inhibits the activity of the methyltransferase PRC2 locally while still prolonging its chromatin binding time. Access all areas: Asymmetric nucleosomes are a key feature of stem cell chromatin. Here a modular and traceless chemical strategy to control the supramolecular assembly of bivalent nucleosomes asymmetrically modified at K27 and K36, is described. It is shown that the trimethylation of K36 hinders PRC2 activity while extending its binding time to chromatin fibers.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.201800744