Glutamic acids get chromatin to loosen up | Chemical & Engineering News
Volume 94 Issue 47 | pp. 10-11 | Concentrates
Issue Date: November 28, 2016

Glutamic acids get chromatin to loosen up

Acidic patch on ubiquitin’s surface plays a key role in altering chromatin structure
Department: Science & Technology
Keywords: epigenetics, chromatin, ubiquitin, glutamic acid

The DNA-packaging material chromatin is made of DNA wrapped around protein spools called histones. These histones control access for copying and transcribing the DNA. Modifying histones with the protein ubiquitin is known to be one way of loosening the chromatin structure to provide access to the DNA. But the mechanism by which ubiquitin achieves this loosening has remained unknown. Tom W. Muir, Galia T. Debelouchina, and Karola Gerecht of Princeton University have reported using cross-linking experiments and hydrogen-deuterium exchange with NMR spectroscopy to figure out what in ubiquitin interacts with chromatin (Nat. Chem. Biol. 2016, DOI: 10.1038/nchembio.2235). Their findings suggest that two glutamic acids on ubiquitin’s surface are the key drivers. The researchers observe that many more cross-links form between ubiquitin and histone proteins when those glutamic acids are present than when they are replaced by other amino acids. In addition, the cross-linking experiments revealed that ubiquitin interacts both with histone proteins and with other copies of itself. The Princeton team proposes that ubiquitin forces chromatin to loosen up by acting as a wedge between neighboring nucleosomes, the repeating unit of chromatin. In addition, the researchers suggest that the ubiquitin-ubiquitin interactions further promote loosening by preventing chromatin fibers from associating with one another.

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In this 12-mer nucleosome array, ubiquitin (purple) binds at locations (black spots) between neighboring nucleosomes (blue/ gold, labeled N1-N12).
Credit: Nat. Chem. Biol.
Model of nucleosome array showing where ubiquitin binds.
 
In this 12-mer nucleosome array, ubiquitin (purple) binds at locations (black spots) between neighboring nucleosomes (blue/ gold, labeled N1-N12).
Credit: Nat. Chem. Biol.
 
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