Model of gene transcriptional regulation dependent on H2A.Z occupancy and its acetylated state in prostate cancer. (A) In a normal cell, genes that are actively transcribed exhibit a bimodal distribution of at least three acetylated H2A.Z nucleosomes plus and minus the TSS. In cancer, some inactivated genes (including TSG), undergo epigenetic change across the promoter that includes deacetylation of H2A.Z nucleosomes, either through active deacetylation or exchange of a H2A.Z nucleosome (depicted as “?”). (B) In contrast, in a normal cell inactive genes contain a mix of H2A and H2A.Z nucleosomes across the entire promoter (H2A/H2A.Z nucleosomes). The apparent mix of H2A or H2A.Z–nucleosomes could be heterotypic nucleosomes containing one H2A dimer and one H2A.Z dimer, or H2A.Z and H2A homotypic nucleosomes deposited alternatively across the promoter. In a cancer cell there is a general loss of H2A.Z nucleosomes, together with a gain of acH2A.Z nucleosomes plus and minus three or more nucleosomes around the TSS, either through active acetylation or exchange of a H2A.Z nucleosome (depicted as “?”), resulting in an overexpression of these genes (e.g., oncogenes).
