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Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9
Open accessAbstract
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.
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Cited by
Histone methylation: a dynamic mark in health, disease and inheritance
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Writing, erasing and reading histone lysine methylations
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Reversal of H3K9me2 by a Small-Molecule Inhibitor for the G9a Histone Methyltransferase
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G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis
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Self-citationHeterochromatin: Guardian of the Genome
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Metadata
- Authors
- Tachibana, M., Ueda, J., Fukuda, M., Takeda, N., Ohta, T., Iwanari, H., Sakihama, T., Kodama, T., Hamakubo, T., & Shinkai, Y.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-03-17
- Volume
- 19
- Issue
- 7
- Pages
- 815-826
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2163771097
- Cited by
- 845
- References
- 4
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Tachibana, M., Ueda, J., Fukuda, M., Takeda, N., Ohta, T., Iwanari, H., Sakihama, T., Kodama, T., Hamakubo, T., & Shinkai, Y. (2005). Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes & Development. https://doi.org/10.1101/gad.1284005
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