title: Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.
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.
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Edyta
authors: E
authors: Marcon
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Zuyao
authors: Z
authors: Ni
authors: Research Institute, Molecular Structure and Function Program, Hospital for Sick Children, 180 Dundas Street, Toronto, ON M5G 1Z8, Canada.
authors: Shuye
authors: S
authors: Pu
authors: Research Institute, Molecular Structure and Function Program, Hospital for Sick Children, 180 Dundas Street, Toronto, ON M5G 1Z8, Canada.
authors: Andrei L
authors: AL
authors: Turinsky
authors: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors: Sandra Smiley
authors: SS
authors: Trimble
authors: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors: Jonathan B
authors: JB
authors: Olsen
authors: Laboratory Medicine and Pathobiology Department, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors: Rosalind
authors: R
authors: Silverman-Gavrila
authors: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors: Lorelei
authors: L
authors: Silverman-Gavrila
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Sadhna
authors: S
authors: Phanse
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Hongbo
authors: H
authors: Guo
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Guoqing
authors: G
authors: Zhong
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Xinghua
authors: X
authors: Guo
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Peter
authors: P
authors: Young
authors: Department of Medical Biophysics, University of Toronto, TMDT, 101 College Street, Toronto, ON M5G 1L7, Canada; The Princess Margaret Cancer Center, University Health Network, 610 University Avenue, Toronto, ON M5G 1L7, Canada.
authors: Swneke
authors: S
authors: Bailey
authors: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors: Denitza
authors: D
authors: Roudeva
authors: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors: Dorothy
authors: D
authors: Zhao
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Johannes
authors: J
authors: Hewel
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors: Joyce
authors: J
authors: Li
authors: Structural Genomics Consortium, University of Toronto, MaRS Centre, 101 College Street, Toronto, ON M5G 1L7, Canada.
authors: Susanne
authors: S
authors: Gräslund
authors: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
authors: Marcin
authors: M
authors: Paduch
authors: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
authors: Anthony A
authors: AA
authors: Kossiakoff
authors: Department of Medical Biophysics, University of Toronto, TMDT, 101 College Street, Toronto, ON M5G 1L7, Canada; The Princess Margaret Cancer Center, University Health Network, 610 University Avenue, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON M5G 0A3, Canada.
authors: Mathieu
authors: M
authors: Lupien
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors: Andrew
authors: A
authors: Emili
authors: Research Institute, Molecular Structure and Function Program, Hospital for Sick Children, 180 Dundas Street, Toronto, ON M5G 1Z8, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors: Shoshana J
authors: SJ
authors: Wodak
authors: Banting and Best Department of Medical Research, University of Toronto, CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Electronic address: jack.greenblatt@utoronto.ca.
authors: Jack
authors: J
authors: Greenblatt
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D020090:Chromosome Segregation; D057809:HEK293 Cells; D056466:Histone Demethylases / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D008565:Membrane Proteins; C000600473:RCCD1 protein, human; D056466:Histone Demethylases; C550342:KDM8 protein, human