Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore.
EMBO J
; 30(2): 328-40, 2011 Jan 19.
Article
en En
| MEDLINE
| ID: mdl-21157429
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autoantígenos
/
Cromatina
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Proteínas Cromosómicas no Histona
/
Histonas
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Centrómero
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Cromosomas Artificiales Humanos
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Epigénesis Genética
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Proteínas de Unión al ADN
Límite:
Humans
Idioma:
En
Revista:
EMBO J
Año:
2011
Tipo del documento:
Article
País de afiliación:
Reino Unido