GSE40111
Stochastic genome - nuclear lamina contacts are linked to histone H3K9 dimethylation (RNA-seq data)
The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel ''molecular contact memory'' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes. Overall design: 12 RNA-seq experiments for 6 samples, each with a biological replicate: m6ATracer-VP16+/DamLaminB1+ m6ATracer-VP16+/DamLaminB1- m6ATracer-VP16-/DamLaminB1- m6ATracer-GFP+/DamLaminB1+ m6ATracer-GFP+/DamLaminB1- m6ATracer-GFP-/DamLaminB1-