RT Journal A1 Chereji, Răzvan V. A1 Eriksson, Peter R. A1 Ocampo, Josefina A1 Prajapati, Hemant K. A1 Clark, David J. T1 Accessibility of promoter DNA is not the primary determinant of chromatin-mediated gene regulation JF Genome Research JO Genome Research YR 2019 FD December 01 VO 29 IS 12 SP 1985 OP 1995 DO 10.1101/gr.249326.119 UL http://genome.cshlp.org/content/29/12/1985.abstract AB DNA accessibility is thought to be of major importance in regulating gene expression. We test this hypothesis using a restriction enzyme as a probe of chromatin structure and as a proxy for transcription factors. We measured the digestion rate and the fraction of accessible DNA at almost all genomic AluI sites in budding yeast and mouse liver nuclei. Hepatocyte DNA is more accessible than yeast DNA, consistent with longer linkers between nucleosomes, suggesting that nucleosome spacing is a major determinant of accessibility. DNA accessibility varies from cell to cell, such that essentially no sites are accessible or inaccessible in every cell. AluI sites in inactive mouse promoters are accessible in some cells, implying that transcription factors could bind without activating the gene. Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation.