Epigenetic posttranslational modifications (PTMs) of histone are critical for the regulation of eukaryotic transcription. Enzymes establishing and maintaining the epigenetic code are called “writer” and “eraser” by creating or removing posttranslational marks, respectively. Readers are specific binding proteins that recognize histone PTMs and mediate epigenetic signaling. The structure of reader domains provides a typical cavity or surface groove that can accommodate a specific epigenetic mark. Interactions between reader domain and the flanking sequence of the modified amino acid allow the protein containing reader domain to distinguish similar epigenetic marks, such as histone lysine mono-, di- and trimethylation.