Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.

TitleHuman-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.
Publication TypeJournal Article
Year of Publication2014
AuthorsMarcon, E., Z. Ni, S. Pu, A. L. Turinsky, S. Smiley Trimble, J. B. Olsen, R. Silverman-Gavrila, L. Silverman-Gavrila, S. Phanse, H. Guo, G. Zhong, X. Guo, P. Young, S. Bailey, D. Roudeva, D. Zhao, J. Hewel, J. Li, S. Gräslund, M. Paduch, A. A. Kossiakoff, M. Lupien, A. Emili, S. J. Wodak, and J. Greenblatt
JournalCell Rep
Volume8
Issue1
Pagination297-310
Date Published2014 Jul 10
ISSN2211-1247
KeywordsCarrier Proteins, Chromatin, Chromosome Segregation, HEK293 Cells, Histone Demethylases, Humans, Membrane Proteins, Protein Binding
Abstract

Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision) network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

DOI10.1016/j.celrep.2014.05.050
Alternate JournalCell Rep
PubMed ID24981860
Grant List092809 / / Wellcome Trust / United Kingdom
8294 / / Canadian Institutes of Health Research / Canada
UO1GM094588 / GM / NIGMS NIH HHS / United States
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