Co-Profiling of Chromatin Occupancy and RNAs in single cells

Elucidating the relationship between cellular heterogeneity in epigenome and gene expression is critical to understand the underlying cellular states and functions. Jointly profiling chromatin occupancy and RNA at the single level is needed for this purpose, which is however not available currently. Therefore, we developed Single-cell co-profiling of chromatin occupancy and RNAs sequencing (scPCOR-seq) for simultaneously profiling genome-wide gene expression and TF/histone bindings in the same cell. By applying scPCOR-seq to human H1 and 293T cells, scPCOR-seq can successfully detect gene expression and PolII bindings in the same cell at the single cell level and identify cell type specific Cis-regulatory elements (CRE). We observed that the cellular variation in PolII bindings is strongly correlated with that in gene expression, which is affected by the location of polII bindings. This suggests that a new mechanism for the source of cellular heterogeneity in gene expression. Overall, our work provides a promising approach to understand the relationships among different omics layers. Jointly Profiling genome-wide PolII binding and gene expression with multiplex indexing tecnique at the single cell level