Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore

Bergmann, J. H., Rodriguez, M. G., Martins, N. M. C., Kimura, H., Kelly, D. A., Masumoto, H., Larionov, V., Jansen, L. E. T., Earnshaw, W. C. (2011) Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. EMBO Journal, 30 (2). pp. 328-340.

[img] PDF (Paper)
Epigenetic_engineering_shows_H3K4me2_is_required_for_HJURP_targeting_and_CENP-A_assembly_on_a_synthetic_human_kinetochore.pdf
Restricted to Repository staff only

Download (2786Kb)
URL: http://www.ncbi.nlm.nih.gov/pubmed/21157429
DOI: 10.1038/emboj.2010.329

Abstract

Kinetochores assemble on distinct ' centrochromatin' containing the histone H3 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 α-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, α-satellite transcription, maintenance of CENP-A levels and kinetochore stability. © 2011 European Molecular Biology Organization | All Rights Reserved.

Item Type: Paper
Uncontrolled Keywords: CENP-A centromere chromatin kinetochore non-coding RNA
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics

organism description > animal > mammal > primates > hominids > human
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > ncRNA
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Spector lab
Depositing User: CSHL Librarian
Date Deposited: 20 Oct 2011 15:44
Last Modified: 01 May 2013 20:12
PMCID: PMC3025471
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15603

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving