MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming

In this study, we have identified a unique type of enhancer element that is bound by the histone variant macroH2A and devoid of the active histone mark H3K27ac through a comprehensive analysis performed using the cis-regulatory elements as recently described in ENCODE 3. To lay the ground for a better understanding of this new enhancer biology, we have surveyed the epigenetic landscape of four cell types (three normal and a cancer cell line) and incorporated the signal of several histone modifications and histone variants to classify enhancer elements, particularly, inactive ones. We validated our novel classification with gene expression signatures and defined a class of inactive enhancers enriched for macroH2a histone variants, which we termed ‘macro-Bound Enhancers’. To determine the relationship between enhancer activity and macroH2A enrichment, we profiled the epigenomes (using ChIP-seq and ATAC-seq) of several cell lines. We also performed single cell profiling in a estrogen responsive breast cancer cell line with and without macroH2A2