Joint profiling of histone modifications and transcriptome in single cells from mouse brain

Genome-wide profiling of histone modifications can reveal not only the location and activity state of regulatory elements, but also the regulatory mechanisms involved in cell-type-specific gene expression during development and disease pathology. Conventional assays to profile histone modifications in bulk tissue lack resolution due to the cellular heterogeneity. Here, we describe an ultra-high throughput method for single-cell joint profiling of histone modifications and transcriptome that could produce cell-type-resolved maps of chromatin state and transcriptome in complex tissues. We used this method to profile five histone modifications jointly with transcriptome in the adult mouse frontal cortex and hippocampus. Integrative analysis of the resulting maps identified distinct groups of genes subject to divergent epigenetic regulatory mechanisms. Our results demonstrate a general approach for comprehensive analysis of chromatin state and gene regulation in complex tissues and provide insights into the gene regulatory processes in major neuron cell types in the mouse. Combined analysis of RNA and histone modifcations in single-cells.