Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N
Open Access
- 21 June 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 11 (7), 896-902
- https://doi.org/10.1038/ncb1899
Abstract
The histone H3 variant CENP-A specifies centromere identity. CENP-N is the first selective binding partner of CENP-A. Inhibition of CENP-N binding to CENP-A or CENP-N depletion prevents the recruitment of the other CENP proteins involved in centromere assembly. Centromeres are specialized chromosomal domains that direct kinetochore assembly during mitosis. CENP-A (centromere protein A), a histone H3-variant present exclusively in centromeric nucleosomes, is thought to function as an epigenetic mark that specifies centromere identity. Here we identify the essential centromere protein CENP-N as the first protein to selectively bind CENP-A nucleosomes but not H3 nucleosomes. CENP-N bound CENP-A nucleosomes in a DNA sequence-independent manner, but did not bind soluble CENP-A–H4 tetramers. Mutations in CENP-N that reduced its affinity for CENP-A nucleosomes caused defects in CENP-N localization and had dominant effects on the recruitment of CENP-H, CENP-I and CENP-K to centromeres. Depletion of CENP-N using siRNA (short interfering RNA) led to similar centromere assembly defects and resulted in reduced assembly of nascent CENP-A into centromeric chromatin. These data suggest that CENP-N interprets the information encoded within CENP-A nucleosomes and recruits other proteins to centromeric chromatin that are required for centromere function and propagation.This publication has 24 references indexed in Scilit:
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