Journal
EMBO JOURNAL
Volume 30, Issue 2, Pages 328-340Publisher
WILEY
DOI: 10.1038/emboj.2010.329
Keywords
CENP-A; centromere; chromatin; kinetochore; non-coding RNA
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Funding
- Wellcome Trust
- Fundacao para a Ciencia e a Tecnologia (FCT)
- Fundacao Calouste Gulbenkian, FCT [BIA-PRO/100537/2008]
- European Commission
- EMBO
- NIH, National Cancer Institute, Center for Cancer Research
- Ministry of Education, Science, Sports and Culture of Japan
- MEXT of Japan
- Grants-in-Aid for Scientific Research [23247030, 21570196] Funding Source: KAKEN
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Kinetochores assemble on distinct 'centrochromatin' containing the histone 113 variant CENP-A and interspersed nucleosomes dimethylated on H3K4 (H3K4me2). Little is known about how the chromatin environment at active centromeres governs centromeric structure and function. Here, we report that centrochromatin resembles K4-K36 domains found in the body of some actively transcribed housekeeping genes. By tethering the lysine-specific demethylase 1 (LSD1), we specifically depleted H3K4me2, a modification thought to have a role in transcriptional memory, from the kinetochore of a synthetic human artificial chromosome (HAC). H3K4me2 depletion caused kinetochores to suffer a rapid loss of transcription of the underlying CL-satellite DNA and to no longer efficiently recruit HJURP, the CENP-A chaperone. Kinetochores depleted of H3K4me2 remained functional in the short term, but were defective in incorporation of CENP-A, and were gradually inactivated. Our data provide a functional link between the centromeric chromatin, a-satellite transcription, maintenance of CENP-A levels and kinetochore stability. The EMBO Journal (2011) 30, 328-340: doi:10.1038/emboj.2010.329; Published online 14 December 2010
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