biostudies-literatureKim JNIDDK NIH HHSNIEHS NIH HHSNIGMS NIH HHS397-403https://www.ebi.ac.uk/biostudies/studies/S-EPMC1456902biostudies-literatureUnknown7(4)The post-translational modification of histones regulates many cellular processes, including transcription, replication and DNA repair. A large number of combinations of post-translational modifications are possible. This cipher is referred to as the histone code. Many of the enzymes that lay down this code have been identified. However, so far, few code-reading proteins have been identified. Here, we describe a protein-array approach for identifying methyl-specific interacting proteins. We found that not only chromo domains but also tudor and MBT domains bind to methylated peptides from the amino-terminal tails of histones H3 and H4. Binding specificity observed on the protein-domain microarray was corroborated using peptide pull-downs, surface plasma resonance and far western blotting. Thus, our studies expose tudor and MBT domains as new classes of methyl-lysine-binding protein modules, and also demonstrates that protein-domain microarrays are powerful tools for the identification of new domain types that recognize histone modifications.EMBO reportsTudor, MBT and chromo domains gauge the degree of lysine methylation.PMC1456902ES07784DK62248GM68804R56 DK062248ES011047U01 ES011047R01 GM068804P30 ES007784R01 DK062248Daniel JEspejo AXia LBedford MTZhang YLake AKim JKrishna MfalseTudor, MBT and chromo domains gauge the degree of lysine methylation.The post-translational modification of histones regulates many cellular processes, including transcription, replication and DNA repair. A large number of combinations of post-translational modifications are possible. This cipher is referred to as the histone code. Many of the enzymes that lay down this code have been identified. However, so far, few code-reading proteins have been identified. Here, we describe a protein-array approach for identifying methyl-specific interacting proteins. We found that not only chromo domains but also tudor and MBT domains bind to methylated peptides from the amino-terminal tails of histones H3 and H4. Binding specificity observed on the protein-domain microarray was corroborated using peptide pull-downs, surface plasma resonance and far western blotting. Thus, our studies expose tudor and MBT domains as new classes of methyl-lysine-binding protein modules, and also demonstrates that protein-domain microarrays are powerful tools for the identification of new domain types that recognize histone modifications.2006-01-01T00:00:00Z2006 Apr2026-03-16T16:10:41.659Z2019-03-27T01:26:23ZS-EPMC14569021641578810.1038/sj.embor.7400625