Methods for the detection of dna-rna proximity in vivo

A method for identifying non-coding RNA-genomic DNA (ncRNA-gDNA) interactions, comprising:

• cross-linking ncRNA and gDNA molecules that are proximate to each other in a cell by applying a cross-linking agent to a biological sample comprising one or more cells or nuclei such that the ncRNA and gDNA that are proximate to each other are held in a fixed position relative to one another;
• lysing the cells or nuclei;
• fragmenting cross-linked ncRNA-gDNA from the fixed cells or nuclei by enzymatic cleavage, chemical cleavage, or mechanical shearing;
• ligating at least one end of the cross-linked and fragmented ncRNA-gDNA to create joined RNA-DNA hybrid molecules;
• reversing the crosslinking;
• reverse transcribing the ligated RNA-DNA hybrid molecules to create joined DNA molecules that retain sequence information of the ncRNA and gDNA in the join;
• detecting cellular ncRNA-gDNA interactions by sequencing the at least one target join DNA molecule, thereby determining the sequence of the ncRNA and the gDNA sequence with which the ncRNA interacts.