α-amino trimethylation of CENP-A by NRMT is required for full recruitment of the centromere

• Published in: Nature communications 2017-03, Vol.8 (1), p.14678-14678, Article 14678
• Main Authors: Sathyan, Kizhakke M., Fachinetti, Daniele, Foltz, Daniel R.
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/109; 13/89; 14; 14/1; 631/337/100/2285; 631/337/103/90; 631/80/641/2002; 64; 82; 82/29; Amines - metabolism; Animals; Cell Proliferation; Cell Survival; Centromere - metabolism; Centromere Protein A - metabolism; Chromosome Segregation; HCT116 Cells; HeLa Cells; Humanities and Social Sciences; Humans; Methylation; Methyltransferases - metabolism; Mice; multidisciplinary; Science; Science (multidisciplinary); Spindle Apparatus - metabolism; Tumor Suppressor Protein p53 - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14678

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. Centromeres are chromosomal domains epigenetically specified by the presence of the CENP-A containing nucleosomes that control chromosome segregation. Here the authors show that α-amino trimethylation of CENP-A by the enzyme NRMT is required for centromere function, faithful chromosome segregation and cell survival.