H3K9 methylation fine-tunes coordination of transcription by regulating the conformational plasticity of chromosomal folding [RNA-Seq]

Despite that stochastic gene expression variations underlie lineage specification and adaptive responses, little is known about the plasticity of 3D chromatin folding and its effects on cell-to-cell transcriptional variability. Employing the Chromatin In Situ Proximity (ChrISP) technique we visualize here developmentally acquired chromosome 11-specific chromatin hubs rich in the repressive H3K9me2 mark that project towards the lamina in single cells. Inhibition of the H3Kme2 methyl-transferase G9a/Glp not only antagonizedperipheral chromatin compaction, but strikingly also induced the emergence of dense chromatin clusters in the nuclear interior. Changes in chromatin organization were accompanied by the spatial re-organization of transcriptional coordination without affecting the overall level of transcription. LOCKs thus topologically insulate active genes at the nuclear periphery, while allowing transcriptional coordination in the rest of the chromosome. We conclude that G9a/Glp controls not only the plasticity of chromatin conformations, but also spatial coordination of transcription to affect cellular gene expression variability. 2 Biological replicates and 2 technical replicates where treated with both G9a Inhibitor and siRNA