Spatial proximity coordinates histone modification and expression of multiple genes

A cell type transition process requires temporally orchestrated global changes of gene expressions despite existence of large extrinsic and intrinsic stochasticity. One such major source of stochasticity is transcriptional bursting, where even under constant levels of trans-regulatory elements genes stochastically switch between a transcriptionally active and an inactive state. Such bursting dynamics may destroy temporal coordination of genes. We integrated datasets of gene expression, histone modification, and chromosome conformation for the mouse nervous system development and TGF-β treated MCF10A cells. We identified that genes having related functions and regulated by common TFs tend to cluster spatially and share similar histone modification patterns. Through a polymer-based model that describes cooperativity in histone modification dynamics, we predict that genes in proximity synchronize their transcriptions by synchronizing their stochastic switching between histone modification states with different transcriptional activities. This hypothesis is supported by analysis of allele-specific single cell RNAseq data, and we are further testing it with single cell FISH and superresolution imaging.