Dynamics of subnuclear chromatin organization during "C. elegans" development : a role for H3K9 methylation

In eukaryotic cells, DNA is packaged into chromatin. This imposes an accessibility barrier to all genetic processes, while at the same time offering the means for tight control. Based on its accessibility, chromatin is divided into transcriptionally active euchromatin and repressed heterochromatin. Interestingly, these two types of chromatin are spatially separated from each other within the nucleus. Euchromatin is located in the nuclear center, whereas heterochromatin is enriched at the nuclear periphery near the nuclear lamina.
In this thesis, I characterized a fluorescence based experimental system to monitor the perinuclear anchoring of heterochromatin during development of the nematode worm C. elegans. Using this system, I searched for the molecular factors needed to sequester silent chromatin at the nuclear periphery and identified two enzymes with histone methyltransferase activity. Both enzymes specifically methylate lysine 9 on histone H3 (H3K9). Interstingly, they do so in a step-wise manner: the first enzyme mono- and di-methylates H3K9. H3K9me1/2 is then used as a substrate for tri-methylation by the second enzyme.
The results shed light the previously uncharacterized mechanism of perinuclear chromatin sequestration and implicate a role for post-translational modifications of chromatin in its subnuclear organization.