The correct folding of DNA within the nucleus is essential to the physiology of all eukaryotic organisms. The establishment of heterochromatic regions ensures programmed repression of selected genes and the formation of important chromosomal structure such as centromeres. Thus, identification of the basic mechanisms of heterochromatin establishment is pivotal to our understanding of the cell. The SUV39 family of histone methyltransferases plays essential roles during embryogenesis and development through methylation of Histone H3 Lysine 9. The study of these enzymes in humans is complicated by the fact that several proteins target the same histone residue to produce H3K9me. In this work, we take advantage of the model system Schizosaccharomyces pombe, which contains only one H3K9 di- and tri-methyltransferase, namely Clr4. The activity of Clr4 at heterochromatic loci relies on the presence and activity of the CLRC complex, an E3 ubiquitin-ligase whose only known target is H3K14, yielding H3K14ub mark. This modification has been proposed to control heterochromatin formation through stimulation of the methyltransferase activity of Clr4. In this thesis, we set out to investigate the molecular basis of H3K14ub-mediated stimulation of Clr4. I was able to show that H3K14ub directly interacts with the catalytic domain of Clr4 and induces an allosteric activation. Using both in vitro and in vivo silencing assays, I was able to show that disruption of the interaction between H3K14ub and Clr4 causes loss of stimulation in vitro, and complete depletion of heterochromatin in vivo. Finally, I was able to show conservation of this crosstalk mechanism in the human SUV39H2 methyltransferase. Taken together, this work sheds light on the role of H3K14ub in heterochromatin formation and suggest that this process could be conserved in higher eukaryotes.