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

Nat Commun. 2017 Mar 7;8:14678. doi: 10.1038/ncomms14678.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amines / metabolism*
  • Animals
  • Cell Proliferation
  • Cell Survival
  • Centromere / metabolism*
  • Centromere Protein A / metabolism*
  • Chromosome Segregation
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Methylation
  • Methyltransferases / metabolism*
  • Mice
  • Spindle Apparatus / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Amines
  • CENPA protein, human
  • Centromere Protein A
  • Tumor Suppressor Protein p53
  • Methyltransferases
  • NTMT1 protein, human