Protocol for bulk and single-nuclei chromatin accessibility quantification in mouse liver tissue

The accessibility of different chromatin regions to transcription factors and other DNA-binding proteins is a critical determinant of cell function. Here, we detail a modified assay for transposase-accessible chromatin sequencing (ATAC-seq) protocol which measures chromatin accessibility genome wide. We describe nuclei isolation, tagmentation, PCR amplification, and pre- and post-sequencing quality control. Our protocol is optimized for the liver, a tissue where nuclei isolation requires distinct steps. We provide two detailed vignettes: one for bulk ATAC-seq and another for single-nuclei ATAC-seq.