Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9
Open Access
- 17 March 2005
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 19 (7), 815-826
- https://doi.org/10.1101/gad.1284005
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.Keywords
This publication has 40 references indexed in Scilit:
- A dimeric viral SET domain methyltransferase specific to Lys27 of histone H3Nature Structural & Molecular Biology, 2003
- Maintenance of Stable Heterochromatin Domains by Dynamic HP1 BindingScience, 2003
- Modulation of Heterochromatin Protein 1 Dynamics in Primary Mammalian CellsScience, 2003
- Purification and Functional Characterization of SET8, a Nucleosomal Histone H4-Lysine 20-Specific MethyltransferaseCurrent Biology, 2002
- The many faces of histone lysine methylationCurrent Opinion in Cell Biology, 2002
- A Complex with Chromatin Modifiers That Occupies E2F- and Myc-Responsive Genes in G 0 CellsScience, 2002
- SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteinsGenes & Development, 2002
- Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factorOncogene, 2002
- The Generation of Monoclonal Antibodies against Human Peroxisome Proliferator-activated Receptors (PPARs)Journal of Atherosclerosis and Thrombosis, 2002
- Loss of the Suv39h Histone Methyltransferases Impairs Mammalian Heterochromatin and Genome StabilityCell, 2001