Format

Send to

Choose Destination
Angew Chem Int Ed Engl. 2016 Feb 18;55(8):2903-6. doi: 10.1002/anie.201510996. Epub 2016 Jan 25.

Traceless Synthesis of Asymmetrically Modified Bivalent Nucleosomes.

Author information

1
Laboratory of Biophysical Chemistry of Macromolecules, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
2
Laboratory of Biophysical Chemistry of Macromolecules, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland. beat.fierz@epfl.ch.

Abstract

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.

KEYWORDS:

PRC2; bivalent domains; chromatin; epigenetics; expressed protein ligation

PMID:
26806951
DOI:
10.1002/anie.201510996
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center