title: Proteomics of a fuzzy organelle: interphase chromatin.
abstract: Chromatin proteins mediate replication, regulate expression, and ensure integrity of the genome. So far, a comprehensive inventory of interphase chromatin has not been determined. This is largely due to its heterogeneous and dynamic composition, which makes conclusive biochemical purification difficult, if not impossible. As a fuzzy organelle, it defies classical organellar proteomics and cannot be described by a single and ultimate list of protein components. Instead, we propose a new approach that provides a quantitative assessment of a protein's probability to function in chromatin. We integrate chromatin composition over a range of different biochemical and biological conditions. This resulted in interphase chromatin probabilities for 7635 human proteins, including 1840 previously uncharacterized proteins. We demonstrate the power of our large-scale data-driven annotation during the analysis of cyclin-dependent kinase (CDK) regulation in chromatin. Quantitative protein ontologies may provide a general alternative to list-based investigations of organelles and complement Gene Ontology.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Georg
authors.initials: G
authors.lastname: Kustatscher
authors.forename: Nadia
authors.initials: N
authors.lastname: Hégarat
authors.forename: Karen L H
authors.initials: KL
authors.lastname: Wills
authors.forename: Cristina
authors.initials: C
authors.lastname: Furlan
authors.forename: Jimi-Carlo
authors.initials: JC
authors.lastname: Bukowski-Wills
authors.forename: Helfrid
authors.initials: H
authors.lastname: Hochegger
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
mesh_terms: D001185:Artificial Intelligence; D018797:Cell Cycle Proteins / Q000145:classification / Q000235:genetics*; D002498:Centrifugation; D002843:Chromatin / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics*; D063990:Gene Ontology; D006801:Humans; D007399:Interphase / Q000235:genetics*; D013058:Mass Spectrometry; D008954:Models, Biological; D058977:Molecular Sequence Annotation; D040901:Proteomics / Q000379:methods*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D018844:Cyclin-Dependent Kinases