Sorting the nuclear proteome

Motivation: Quantitative experimental analyses of the nuclear interior reveal a morphologically structured yet dynamic mix of membraneless compartments. Major nuclear events depend on the functional integrity and timely assembly of these intra-nuclear compartments. Yet, unknown drivers of protein mobility ensure that they are in the right place at the time when they are needed. Results: This study investigates determinants of associations between eight intra-nuclear compartments and their proteins in heterogeneous genome-wide data. We develop a model based on a range of candidate determinants, capable of mapping the intra-nuclear organization of proteins. The model integrates protein interactions, protein domains, post-translational modification sites and protein sequence data. The predictions of our model are accurate with a mean AUC (over all compartments) of 0.71. We present a complete map of the association of 3567 mouse nuclear proteins with intra-nuclear compartments. Each decision is explained in terms of essential interactions and domains, and qualified with a false discovery assessment. Using this resource, we uncover the collective role of transcription factors in each of the compartments. We create diagrams illustrating the outcomes of a Gene Ontology enrichment analysis. Associated with an extensive range of transcription factors, the analysis suggests that PML bodies coordinate regulatory immune responses.