PU.1 is a pioneer factor that opens up closed chromatin and recruits additional epigenetic modifiers to regulate hematopoiesis and fibrosis.[18, 19] Nucleosome occupancy analysis by NucleoATAC[41] demonstrated that nucleosomes are depleted around the putative PU.1 binding motifs in liver metastasis‐enriched open chromatin regions; conversely, there is little nucleosome remodeling in the primary CRC cells or in regions constitutively open in both primary CRC and liver metastases (Figure 4C). This evidence concerns the gene SPI1 and colorectal carcinoma.