The biological process of differentiation - from a fertilized egg to a human being - is a consecutive mechanism that leads to the establishment of tissue-specific gene expression, but also to a coordinated shut-down of all those genes that are not necessary for a given cell type. This process is accompanied by posttranslational modifications of the chromatin (DNA methylation and covalent histone modifications), also termed the "epigenetic layer". All epigenetic processes are mediated by protein complexes that either mediate specific DNA methylation patterns, or modify nucleosomal proteins in a covalent fashion (acetylation, methylation, phosphorylation and ubiquitinylation). One important player involved in epigenetics is the MLL protein which represents a histone H3 methyltransferase. The MLL gene gained much attention because of its frequent genetic rearrangements, thereby creating oncogenic MLL fusion genes that cause acute leukemia in pediatric and adult patients. This article is summarizing certain functional aspects about MLL, but is mainly emphasizing on an alternative splice event within the PHD domain. This changes the biological properties of the MLL protein, thereby influencing its ability of being either a transcriptional activator or repressor.