Knowledge of protein domains that function as the biological effectors for 
diverse post-translational modifications of histones is critical for 
understanding how nuclear and epigenetic programs are established. Indeed, 
mutations of chromatin effector domains found within several proteins are 
associated with multiple human pathologies, including cancer and 
immunodeficiency syndromes. To date, relatively few effector domains have been 
identified in comparison to the number of modifications present on histone and 
non-histone proteins. Here we describe the generation and application of human 
modified peptide microarrays as a platform for high-throughput discovery of 
chromatin effectors and for epitope-specificity analysis of antibodies commonly 
utilized in chromatin research. Screening with a library containing a majority 
of the Royal Family domains present in the human proteome led to the discovery 
of TDRD7, JMJ2C, and MPP8 as three new modified histone-binding proteins. Thus, 
we propose that peptide microarray methodologies are a powerful new tool for 
elucidating molecular interactions at chromatin.