title: α-amino trimethylation of CENP-A by NRMT is required for full recruitment of the centromere.
abstract: Centromeres are unique chromosomal domains that control chromosome segregation, and are epigenetically specified by the presence of the CENP-A containing nucleosomes. CENP-A governs centromere function by recruiting the constitutive centromere associated network (CCAN) complex. The features of the CENP-A nucleosome necessary to distinguish centromeric chromatin from general chromatin are not completely understood. Here we show that CENP-A undergoes α-amino trimethylation by the enzyme NRMT in vivo. We show that α-amino trimethylation of the CENP-A tail contributes to cell survival. Loss of α-amino trimethylation causes a reduction in the CENP-T and CENP-I CCAN components at the centromere and leads to lagging chromosomes and spindle pole defects. The function of p53 alters the response of cells to defects associated with decreased CENP-A methylation. Altogether we show an important functional role for α-amino trimethylation of the CENP-A nucleosome in maintaining centromere function and faithful chromosomes segregation.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Kizhakke M
authors.initials: KM
authors.lastname: Sathyan
authors.affiliation: Department of Cell Biology and Cancer, Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, Paris 75005, France.
authors.forename: Daniele
authors.identifier: 0000-0002-8795-6771
authors.initials: D
authors.lastname: Fachinetti
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA.|Northwestern University, Feinberg School of Medicine, Department of Biochemistry and Molecular Genetics, Chicago, Illinois 60611, USA.|Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Foltz
mesh_terms: D000588:Amines / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A / Q000378:metabolism*; D020090:Chromosome Segregation; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D008941:Spindle Apparatus / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000588:Amines; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D016159:Tumor Suppressor Protein p53; D008780:Methyltransferases; C551913:NTMT1 protein, human