Tudor, 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.
Kim
Jeesun
J
The University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville, 78957, USA.
Daniel
Jeremy
J
Espejo
Alexsandra
A
Lake
Aimee
A
Krishna
Murli
M
Xia
Li
L
Zhang
Yi
Y
Bedford
Mark T
MT
D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D040081:Protein Array Analysis; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D006657:Histones; D008239:Lysine