Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding

Aleksandra Skrajna, Dennis Goldfarb, Katarzyna M. Kedziora, Emily M. Cousins, Gavin D. Grant, Cathy J. Spangler, Emily H. Barbour, Xiaokang Yan, Nathaniel A. Hathaway, Nicholas G. Brown, Jeanette G. Cook, Michael B. Major, Robert K. McGinty

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While studies of individual nucleosome interactions have suggested that an acidic patch on the nucleosome disk may be a common site for recruitment to chromatin, the pervasiveness of acidic patch binding and whether other nucleosome binding hot-spots exist remain unclear. Here, we use nucleosome affinity proteomics with a library of nucleosomes that disrupts all exposed histone surfaces to comprehensively assess how proteins recognize nucleosomes. We find that the acidic patch and two adjacent surfaces are the primary hot-spots for nucleosome disk interactions, whereas nearly half of the nucleosome disk participates only minimally in protein binding. Our screen defines nucleosome surface requirements of nearly 300 nucleosome interacting proteins implicated in diverse nuclear processes including transcription, DNA damage repair, cell cycle regulation and nuclear architecture. Building from our screen, we demonstrate that the Anaphase-Promoting Complex/Cyclosome directly engages the acidic patch, and we elucidate a redundant mechanism of acidic patch binding by nuclear pore protein ELYS. Overall, our interactome screen illuminates a highly competitive nucleosome binding hub and establishes universal principles of nucleosome recognition.

Original languageEnglish
Pages (from-to)9415-9432
Number of pages18
JournalNucleic acids research
Volume48
Issue number17
DOIs
StatePublished - Sep 25 2020
Externally publishedYes

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