Cell Reports
(Jul 2014)
Human-Chromatin-Related Protein Interactions Identify a Demethylase Complex Required for Chromosome Segregation
Edyta Marcon,
Zuyao Ni,
Shuye Pu,
Andrei L. Turinsky,
Sandra Smiley Trimble,
Jonathan B. Olsen,
Rosalind Silverman-Gavrila,
Lorelei Silverman-Gavrila,
Sadhna Phanse,
Hongbo Guo,
Guoqing Zhong,
Xinghua Guo,
Peter Young,
Swneke Bailey,
Denitza Roudeva,
Dorothy Zhao,
Johannes Hewel,
Joyce Li,
Susanne Gräslund,
Marcin Paduch,
Anthony A. Kossiakoff,
Mathieu Lupien,
Andrew Emili,
Shoshana J. Wodak,
Jack Greenblatt
Affiliations
Edyta Marcon
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Zuyao Ni
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Shuye Pu
Research Institute, Molecular Structure and Function Program, Hospital for Sick Children, 180 Dundas Street, Toronto, ON M5G 1Z8, Canada
Andrei L. Turinsky
Research Institute, Molecular Structure and Function Program, Hospital for Sick Children, 180 Dundas Street, Toronto, ON M5G 1Z8, Canada
Sandra Smiley Trimble
Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada
Jonathan B. Olsen
Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada
Rosalind Silverman-Gavrila
Laboratory Medicine and Pathobiology Department, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada
Lorelei Silverman-Gavrila
Department of Physiology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada
Sadhna Phanse
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Hongbo Guo
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Guoqing Zhong
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Xinghua Guo
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Peter Young
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Swneke Bailey
Department of Medical Biophysics, University of Toronto, TMDT, 101 College Street, Toronto, ON M5G 1L7, Canada
Denitza Roudeva
Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada
Dorothy Zhao
Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada
Johannes Hewel
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Joyce Li
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Susanne Gräslund
Structural Genomics Consortium, University of Toronto, MaRS Centre, 101 College Street, Toronto, ON M5G 1L7, Canada
Marcin Paduch
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
Anthony A. Kossiakoff
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
Mathieu Lupien
Department of Medical Biophysics, University of Toronto, TMDT, 101 College Street, Toronto, ON M5G 1L7, Canada
Andrew Emili
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
Shoshana J. Wodak
Research Institute, Molecular Structure and Function Program, Hospital for Sick Children, 180 Dundas Street, Toronto, ON M5G 1Z8, Canada
Jack Greenblatt
Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada
DOI
https://doi.org/10.1016/j.celrep.2014.05.050
Journal volume & issue
Vol. 8,
no. 1
pp.
297
– 310
Abstract
Read online
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.
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