A case study in cross-talk: The histone lysine methyltransferases G9a and GLP

Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520, USA.
Nucleic Acids Research (Impact Factor: 9.11). 02/2010; 38(11):3503-11. DOI: 10.1093/nar/gkq081
Source: PubMed


The histone code hypothesis predicts that the post-translational modification of histones can bring about distinct chromatin states, and it therefore serves a key regulatory role in chromatin biology. The impact of one mark on another has been termed cross-talk. Some marks are mutually exclusive, while others act in concert. As multiple marks contributing to one outcome are generally brought about by complexes containing multiple catalytic and binding domains, it appears regulation of chromatin involves a web of writers and readers of histone modifications, chromatin remodeling activities and DNA methylation. Here, we focus on the protein lysine methyltransferases G9a and GLP as examples of this extended cross-talk. G9a and GLP can catalyze the formation of and bind to the same methyl mark via distinct domains. We consider the impact of other histone modifications on G9a/GLP activity and the coordination of activities within G9a/GLP containing complexes. We evaluate the potential impact of product binding on product specificity and on maintenance and propagation of the methyl mark. Lastly, we examine the recruitment of other silencing factors by G9a/GLP. Regulated assembly of specific complexes around key marks may reinforce or alter the biological outcome associated with given histone modifications.

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    • "G9a, along with its partner protein GLP, is crucial for H3K9 (mainly H3K9me and H3K9me2) methylation of euchromatin and is involved in transcriptional silencing [19,20]. G9a binds to its own product, H3K9me and H3K9me2 residues, through its ankyrin domain, a mechanism suggested to play a role in propagation of H3K9 methylation through cell divisions [21,22]. Recent studies have shown that G9a physically interacts with Dnmt3a/3b and recruits them to G9a-target gene promoters, retrotransposons and major satellite repeats for de novo methylation in ES cells [23], independent of its histone methyltransferase activity [24]. "
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