Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9.

By M. Tachibana, Jun Ueda, Mikiko Fukuda, N. Takeda, T. Ohta, H. Iwanari, T. Sakihama, T. Kodama, T. Hamakubo, Y. Shinkai. Genes & Development, 2005

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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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0a70c21efe31c02ace24787aa11aecaf2c399ee8

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Citations in the corpus

• Single-cell dynamics of genome-nuclear lamina interactions. (2013, methodology): “We used RNA interference (RNAi) to knock down G9a and confirmed that this lowered the overall H3K9me2 levels (Figures S4B and S4D), as was reported previously (Tachibana et al., 2005; Yokochi et al., 2009).”
• Histone Marks in the 'Driver's Seat': Functional Roles in Steering the Transcription Cycle. (2017, background): “H3K9me2 is typically associated with heterochromatin formation and can be generated for gene silencing on active genes [87,88].”
• How is pluripotency determined and maintained? (2007, background): “5 NT Normal Normal Defective Restored Lei et al., 1996; Gaudet et al., 1998 Dnmt3a/3b Die at E11.”
• G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis (2006, background): “For reversal experiments, wild-type, G9a –/– (clones 10–20, 2–3) and G9a –/– Tg ES cells, as well as Dnmt3a / 3b –/–15,19 , were induced to differentiate with 1 µ M 1d). bp, base pairs.”
• The interplay of histone modifications – writers that read (2015, neutral): “The heterodimeric complex of G9a and GLP catalyzes H3K9me1 and H3K9me2 modifications [109], which are mainly associated with transcriptional silencing but also occur in euchromatic regions [110].”
• The diverse functions of histone lysine methylation (2005, background): “Mice that are deficient in G9a or G9a-related protein (GLP), two highly related histone methyltrans-ferases, exhibit severely reduced H3-K9 methylation in euchromatic regions, which indicates that G9a and GLP are the primary H3-K9 methyltransferases in these chromatin domains 52 .”