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PMID:15774718

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Citation

Tachibana, M, Ueda, J, Fukuda, M, Takeda, N, Ohta, T, Iwanari, H, Sakihama, T, Kodama, T, Hamakubo, T and Shinkai, Y (2005) Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev. 19:815-26

Abstract

Histone H3 Lys 9 (H3-K9) methylation is a crucial epigenetic mark for transcriptional silencing. G9a is the major mammalian H3-K9 methyltransferase that targets euchromatic regions and is essential for murine embryogenesis. There is a single G9a-related methyltransferase in mammals, called GLP/Eu-HMTase1. Here we show that GLP is also important for H3-K9 methylation of mouse euchromatin. GLP-deficiency led to embryonic lethality, a severe reduction of H3-K9 mono- and dimethylation, the induction of Mage-a gene expression, and HP1 relocalization in embryonic stem cells, all of which were phenotypes of G9a-deficiency. Furthermore, we show that G9a and GLP formed a stoichiometric heteromeric complex in a wide variety of cell types. Biochemical analyses revealed that formation of the G9a/GLP complex was dependent on their enzymatic SET domains. Taken together, our new findings revealed that G9a and GLP cooperatively exert H3-K9 methyltransferase function in vivo, likely through the formation of higher-order heteromeric complexes.

Links

PubMed PMC1074319 Online version:10.1101/gad.1284005

Keywords

Animals; Euchromatin/enzymology; Histone-Lysine N-Methyltransferase/chemistry; Histone-Lysine N-Methyltransferase/metabolism; Histones/metabolism; Lysine/metabolism; Methylation; Mice; Protein Methyltransferases; Protein Structure, Quaternary; Stem Cells/enzymology

Significance

Annotations

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

MOUSE:EHMT1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:EHMT1

enables

GO:0046974: histone methyltransferase activity (H3-K9 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:EHMT1

enables

GO:0046976: histone methyltransferase activity (H3-K27 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:EHMT1

involved_in

GO:0045995: regulation of embryonic development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EHMT1

involved_in

GO:0018026: peptidyl-lysine monomethylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EHMT1

involved_in

GO:0018027: peptidyl-lysine dimethylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EHMT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Z148

F

Seeded From UniProt

complete

MOUSE:EHMT2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:EHMT2

enables

GO:0046974: histone methyltransferase activity (H3-K9 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:EHMT2

enables

GO:0046976: histone methyltransferase activity (H3-K27 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:EHMT2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q5DW34

F

Seeded From UniProt

complete


See also

References

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