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PMID:16717091

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Citation

Etchegaray, JP, Yang, X, DeBruyne, JP, Peters, AH, Weaver, DR, Jenuwein, T and Reppert, SM (2006) The polycomb group protein EZH2 is required for mammalian circadian clock function. J. Biol. Chem. 281:21209-15

Abstract

We examined the importance of histone methylation by the polycomb group proteins in the mouse circadian clock mechanism. Endogenous EZH2, a polycomb group enzyme that methylates lysine 27 on histone H3, co-immunoprecipitates with CLOCK and BMAL1 throughout the circadian cycle in liver nuclear extracts. Chromatin immunoprecipitation revealed EZH2 binding and di- and trimethylation of H3K27 on both the Period 1 and Period 2 promoters. A role of EZH2 in cryptochrome-mediated transcriptional repression of the clockwork was supported by overexpression and RNA interference studies. Serum-induced circadian rhythms in NIH 3T3 cells in culture were disrupted by transfection of an RNA interfering sequence targeting EZH2. These results indicate that EZH2 is important for the maintenance of circadian rhythms and extend the activity of the polycomb group proteins to the core clockwork mechanism of mammals.

Links

PubMed Online version:10.1074/jbc.M603722200

Keywords

ARNTL Transcription Factors; Animals; Basic Helix-Loop-Helix Transcription Factors/chemistry; CLOCK Proteins; Circadian Rhythm; DNA-Binding Proteins/physiology; HeLa Cells; Histones/chemistry; Humans; Liver/metabolism; Lysine/chemistry; Mice; Mice, Inbred BALB C; NIH 3T3 Cells; Polycomb Repressive Complex 2; Promoter Regions, Genetic; Trans-Activators/metabolism; Transcription Factors/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CLOCK

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9R194

F

Seeded From UniProt

complete

MOUSE:CLOCK

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O54943

F

Seeded From UniProt

complete

MOUSE:CLOCK

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O35973

F

Seeded From UniProt

complete

MOUSE:CLOCK

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97784

F

Seeded From UniProt

complete

MOUSE:CLOCK

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61188

F

Seeded From UniProt

complete

MOUSE:PER1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O08785

F

Seeded From UniProt

complete

MOUSE:PER1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WTL8

F

Seeded From UniProt

complete

MOUSE:PER2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O08785

F

Seeded From UniProt

complete

MOUSE:PER2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WTL8

F

Seeded From UniProt

complete

MOUSE:CRY1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O08785

F

Seeded From UniProt

complete

MOUSE:CRY1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WTL8

F

Seeded From UniProt

complete

MOUSE:CRY1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61188

F

Seeded From UniProt

complete

MOUSE:EZH2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97784

F

Seeded From UniProt

complete

MOUSE:EZH2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WTL8

F

Seeded From UniProt

complete

MOUSE:EZH2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O08785

F

Seeded From UniProt

complete

MOUSE:EZH2

involved_in

GO:0070734: histone H3-K27 methylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EZH2

involved_in

GO:0042752: regulation of circadian rhythm

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EZH2

enables

GO:0000979: RNA polymerase II core promoter sequence-specific DNA binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CRY2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WTL8

F

Seeded From UniProt

complete

MOUSE:CRY2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O08785

F

Seeded From UniProt

complete

MOUSE:BMAL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9R194

F

Seeded From UniProt

complete

MOUSE:BMAL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O54943

F

Seeded From UniProt

complete

MOUSE:BMAL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O35973

F

Seeded From UniProt

complete

MOUSE:BMAL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97784

F

Seeded From UniProt

complete

MOUSE:BMAL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61188

F

Seeded From UniProt

complete

HUMAN:EZH2

involved_in

GO:0042752: regulation of circadian rhythm

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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