The paper, Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding, was designated as a “Breakthrough Article” by NAR in 2020 which is an honor given to the top 1-2% of all papers.
The nucleosome is the fundamental packaging unit of our genome. Proteins that control gene expression and repair of DNA damage must bind to nucleosomes to perform their functions. While studies of individual proteins bound to the nucleosome have shown that an acidic patch made of negatively charged atoms on the nucleosome may be a common site for protein binding, the pervasiveness of this acidic patch binding and whether other nucleosome binding hot-spots exist remained unclear. This study describes an elegant proteomics screen that establishes the universal principles of nucleosome recognition. The authors prepared a library of nucleosomes, each containing a cluster of mutations within a different patch on the nucleosome disk surface. Quantitative mass spectrometry was then used to compare the abundance of proteins that interact with each of the nucleosomes in the library. By analyzing how each cluster of mutations influenced nucleosome binding proteome-wide, the authors paired hundreds of nucleosome binding proteins with the specific nucleosome surface requirements. The nucleosome acidic patch, was critical for the majority of nucleosome binding proteins, often in concert with two adjacent, newly identified hot-spots. This comprehensive nucleosome interactome screen uncovers the general rules governing recognition of the fundamental unit of the genome.
Aleksandra Skrajna PhD is an American Cancer Society postdoctoral fellow in the McGinty lab.
Link to publication document: Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding (July 07, 2020)
Link to breakthrough publication document: 2020 Breakthrough articles from Nucleic Acids Research: (Fall 2020)