Chromatin found in space

Methods to map chromatin accessibility are used to probe the role of the chromatin landscape in shaping cellular states and how they can evolve. However, the methods generally require tissue dissociation, and most information about spatial context is lost. Writing in Nature, the labs of Rong Fan and Gonçalo Castelo-Branco now present spatial-ATAC-seq, a method for genome-wide mapping of chromatin accessibility in tissues with high-spatial cellular resolution. The Tn5 transposition step is performed on fixed tissue sections, with adapters containing a ligation linker inserted into accessible genomic loci. This is followed by two rounds of in situ ligation with DNA barcodes delivered using microchannels to define the spatial x–y coordinates of nuclei. Next, the tissues are imaged to correlate the spatially barcoded accessible chromatin with its morphology. Reverse crosslinking releases the barcoded DNA fragments to be amplified for library preparation.

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