Extended Data Fig. 1: Overview of the MUSIC method.

(a) An example chromatin complex with one associated DNA fragment (blue) and one RNA molecule (red) is shown to illustrate the procedure. Other chromatin complexes with any number of associated DNA fragments or RNA molecules are expected to react accordingly. The RNA Linker with half single strand RNA (ssRNA, red) and half single strand DNA (ssDNA, purple). (b) The ligation product with a RNA linker conjugates with the Y-shaped DNA Linker that contains a double strand region (dsDNA) and single strand regions (top-ssDNA and bottom-ssDNA). (c) The ligation product with both DNA and RNA linkers. (d-e) Addition of the three sets of Cell Barcodes (color coded in black, yellow, green) and A-tail. (f) Reaction in a 10X GEM system. (g) Aliquoting the output of the 10X GEM system for library preparation. (h) The sequence configuration of the constructed sequencing library. For Illumina paired-end sequencing, Read1 covers the 28 bp 10X Barcode that consists of a 16 bp 10X GEM Barcode and 12 bp 10X UMI. Index 1 covers the 8 bp I7 Barcode, and Read2 covers the Cell Barcodes as well as the RNA Linker and the RNA insert or the DNA Linker and the DNA insert.