Journal
DEVELOPMENTAL CELL
Volume 29, Issue 6, Pages 740-749Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2014.05.001
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- Wellcome Trust [073915]
- Precursory Research for Embryonic Science and Technology of the Japan Science and Technology Agency
- MEXT
- Transdisciplinary Research Integration Center (TRIC) of Research Organization of Information and Systems
- [077707]
- [092076]
- Grants-in-Aid for Scientific Research [26440190, 25116002] Funding Source: KAKEN
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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.
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