DNA Sequence-Specific Binding of CENP-B Enhances the Fidelity of Human Centromere Function

Dev Cell. 2015 May 4;33(3):314-27. doi: 10.1016/j.devcel.2015.03.020.


Human centromeres are specified by a stably inherited epigenetic mark that maintains centromere position and function through a two-step mechanism relying on self-templating centromeric chromatin assembled with the histone H3 variant CENP-A, followed by CENP-A-dependent nucleation of kinetochore assembly. Nevertheless, natural human centromeres are positioned within specific megabase chromosomal regions containing α-satellite DNA repeats, which contain binding sites for the DNA sequence-specific binding protein CENP-B. We now demonstrate that CENP-B directly binds both CENP-A's amino-terminal tail and CENP-C, a key nucleator of kinetochore assembly. DNA sequence-dependent binding of CENP-B within α-satellite repeats is required to stabilize optimal centromeric levels of CENP-C. Chromosomes bearing centromeres without bound CENP-B, including the human Y chromosome, are shown to mis-segregate in cells at rates several-fold higher than chromosomes with CENP-B-containing centromeres. These data demonstrate a DNA sequence-specific enhancement by CENP-B of the fidelity of epigenetically defined human centromere function.

Publication types

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

MeSH terms

  • Animals
  • Autoantigens / metabolism*
  • Binding Sites / genetics
  • Centromere / metabolism*
  • Centromere Protein A
  • Centromere Protein B / genetics
  • Centromere Protein B / metabolism*
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA, Satellite / metabolism*
  • Histones / metabolism
  • Humans


  • Autoantigens
  • CENPA protein, human
  • CENPB protein, human
  • Centromere Protein A
  • Centromere Protein B
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA, Satellite
  • Histones
  • centromere protein C