Final Activity Report Summary - REMETNET (Repressive histone methylation networks) Histone modifications play a key role in epigenetic regulation and affect genome integrity, transcriptional regulation, development, diseases and cancer. Some of these modifications can be easily removed while others, especially histone lysine methylation, were thought to be more stable. Specific modifications are enriched at active or accessible euchromatin, while others accumulate on repressed heterochromatin. Our objective was to identify novel regulators and components of heterochromatin. We collaborated with Gunter Reuter's laboratory to map and identify such factors in drosophila melanogaster and, in the next step, to study their mammalian orthologs. As a complementary approach, we also developed a localisation screen in mammalian cells to search for factors enriched at heterochromatin. We identified several known and novel players regulating heterochromatin using both approaches. One group of these regulators was jmjC domain proteins. We studied the mammalian Jmjd2 group in detail, and found that these proteins were histone lysine demethylases. These enzymes could demethylate even the most stable trimethyl state of histone lysine residues at specific positions. As a result, our finding pointed towards the plasticity of histone lysine methylation.