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Dev Cell. 2014 Jun 23;29(6):740-9. doi: 10.1016/j.devcel.2014.05.001.

Histone H4 Lys 20 monomethylation of the CENP-A nucleosome is essential for kinetochore assembly.

Author information

1
Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan.
2
Comparative Genomics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
3
Cell Innovation Project, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
4
Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
5
Comparative Genomics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan; National Institute of Informatics, Hitotsubashi, Chiyoda-ku, Tokyo 101-8430, Japan.
6
Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
7
Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan. Electronic address: tfukagaw@lab.nig.ac.jp.

Abstract

In vertebrate cells, centromeres are specified epigenetically through the deposition of the centromere-specific histone CENP-A. Following CENP-A deposition, additional proteins are assembled on centromeric chromatin. However, it remains unknown whether additional epigenetic features of centromeric chromatin are required for kinetochore assembly. Here, we used ChIP-seq analysis to examine centromere-specific histone modifications at chicken centromeres, which lack highly repetitive sequences. We found that H4K20 monomethylation (H4K20me1) is enriched at centromeres. Immunofluorescence and biochemical analyses revealed that H4K20me1 is present at all centromeres in chicken and human cells. Based on immunoprecipitation data, H4K20me1 occurs primarily on the histone H4 that is assembled as part of the CENP-A nucleosome following deposition of CENP-A into centromeres. Targeting the H4K20me1-specific demethylase PHF8 to centromeres reduces the level of H4K20me1 at centromeres and results in kinetochore assembly defects. We conclude that H4K20me1 modification of CENP-A nucleosomes contributes to functional kinetochore assembly.

PMID:
24960696
PMCID:
PMC4081567
DOI:
10.1016/j.devcel.2014.05.001
[Indexed for MEDLINE]
Free PMC Article

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