He and his team cloned and characterized mammalian orthologs of dominant Drosophila PEV modifier factors containing the evolutionarily conserved SET domain,[12][13] originally identified by the laboratory of Gunter Reuter.

[14] The SET domain is present in Su(var)3–9, Enhancer of zeste and Trithorax proteins, all of which had been implicated in epigenetic regulation without evidence of enzymatic activity.

[15] This insight, together with refined bioinformatic interrogation revealing a distant relationship of the SET domain with plant methyltransferases, suggested the critical experiment: to test recombinant SUV39H1 for KMT activity on histone substrates.

Genome-wide maps for Suv39h-dependent H3K9me3 marks and Hiseq RNA sequencing revealed a novel role for the Suv39h KMT in the silencing of repeat elements (e.g. LINE and ERV retrotransposons) in mouse embryonic stem cells.

[22] The demonstration that the pericentric major satellite repeats have embedded transcription factor (TF) binding sites that are relevant for TF-mediated recruitment of Suv39h enzymes has provided a general targeting mechanism for the formation of heterochromatin.

[24] The impact of the discovery of the first KMT and its associated functions has been so broad that it stimulated novel lines of research spanning nearly all aspects of chromatin biology and epigenetic control for both basic and applied questions.

[7] Histone lysine methylation has opened molecular insights for the organization of the inactive X chromosome, telomeres and the rDNA cluster and is a crucial mechanism for Polycomb- and Trithorax-mediated gene regulation.