DNA accessibility is not the primary determinant of chromatin-mediated gene regulation (mouse)

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 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, and indicating that DNA accessibility is primarily determined by nucleosome spacing. Remarkably, AluI sites in inactive mouse promoters are accessible in some cells. Furthermore, euchromatin and heterochromatin have very similar accessibilities. Cell-to-cell heterogeneity in DNA accessibility has implications for chromatin models of gene regulation: a transcription factor binding site is blocked in some cells, but not in all cells, guaranteeing neither activation nor repression. Nuclei were prepared from homogenised liver and digested with increasing amounts of the restriction enzyme AluI.