In situ analysis of chromatin interaction

A method, comprising:

• (a) contacting a sample with a first chromatin accessing probe and a second chromatin accessing probe simultaneously or sequentially in either order, wherein:
• the sample comprises a first chromatin region and a second chromatin region, wherein the first chromatin region and the second chromatin region are separated by a genomic distance of at least 0.5 kilobases (kb), and wherein the first and second chromatin regions interact with each other in a cell and are in the same chromosome in the cell, and
• the first chromatin accessing probe hybridizes to the complementary strand of a first nucleic acid strand in the first chromatin region and the second chromatin accessing probe hybridizes to the complementary strand of a second nucleic acid strand in the second chromatin region,
• thereby allowing access for binding to the first and second nucleic acid strands;
• (b) contacting the sample with a first detection probe and a second detection probe simultaneously or sequentially in either order, wherein:
• the first detection probe hybridizes to the first nucleic acid strand and the second detection probe hybridizes to the second nucleic acid strand;
• (c) contacting the sample with a first bridging probe that bridges the 3′ end of the first detection probe and the 5′ end of the second detection probe, and a second bridging probe that bridges the 3′ end of the second detection probe and the 5′ end of the first detection probe;
• (d) circularizing the first and second bridging probes using the first and second detection probes as templates to form a circular probe, wherein the circular probe comprises a sequence of the first nucleic acid strand and a sequence of the second nucleic acid strand;
• (e) generating a rolling circle amplification (RCA) product of the circular probe in situ in the sample;
• and
• (f) detecting the RCA product.