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. [Display omitted] •ATAC-seq is a powerful technique to quantify accessible chromatin genome wide•We designed a protocol to address the special requirements of ATAC-seq for liver tissue•We provide two vignettes: one for bulk ATAC-seq and another for single-nuclei ATAC-seq•Special emphasis is put on isolation of high-quality nuclei preparation Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. 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.