Coupling between adhesome assembly and 3D chromatin organization

Proteins on the cell membrane cluster to respond to extracellular signals; for example, adhesion proteins cluster to enhance extracellular matrix sensing. The maturation of such receptor clusters may require additional adhesome proteins to adapt and reinforce extracellular signal sensing. However, it has been unclear whether the genes encoding these proteins share a spatial organization in the nucleus. Using the adhesome as an example, we show that subsets of genes that code for adhesome proteins exhibit relative spatial clustering and co-regulation in distinct locations within the nucleus. We use Hi-C maps and RNA-seq data from adherent cells to map the correspondence between adhesome gene localization and their expression. Interestingly, we find that the genes encoding several transcription factors, cofactors, and chromatin regulators that regulate these genes are also co-localized with the adhesome gene loci, thereby potentially suggesting a link between the extracellular matrix sensing machinery and gene expression. Additionally, we validate the spatial sub-clustering of adhesome gene loci using MERFISH data and DNA-FISH experiments. Collectively, our results support an association between adhesome gene organization and regulatory state, with a possible role in cellular signal sensing.