Nucleosomes form the fundamental repeating units of eukaryotic chromatin, which are used to pack the large eukaryotic genome into the nucleus while still ensuring appropriate access to it. They are thought to carry epigenetically inherited information in the form of covalent post-translational modifications of core histones, such as acetylation, methylation, phosphorylation, sumoylation and ubiquitynation. These modifications are possible due to the N-terminal tails of the histones, which are unstructured and protrude outward from the nucleosome core. Some of those modifications can directly influence chromatin structure or can be bound and 'read' by histone recognition modules found in many proteins and protein complexes acting on chromatin. It is now well known that many of the histone modifications play a crucial role in regulation of a diverse set of biological processes [1-2]. For example, lysine methylation is coupled to the regulation of transcription by RNA polymerase II (RNApII), X-chromosome inactivation, heterochromatin formation and gene silencing. Methylations at particular histone residues are mostly correlated with either activation or repression of transcription. In our study we are interested in histone H3 modifications, particularly of lysine 4 methylations, which are enriched at actively transcribed gene regions [3-5]. Here we would like to present our structural data and binding assays, which characterize the recognition of the H3K4me2 and H3K4me3 by Set3PHD.