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Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP‐A assembly on a synthetic human kinetochore
Author(s) -
Bergmann Jan H,
Rodríguez Mariluz Gómez,
Martins Nuno M C,
Kimura Hiroshi,
Kelly David A,
Masumoto Hiroshi,
Larionov Vladimir,
Jansen Lars E T,
Earnshaw William C
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.329
Subject(s) - biology , kinetochore , epigenetics , microbiology and biotechnology , computational biology , genetics , gene , chromosome
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.