a, Regular HiChIP (contacts per million), H3K27ac ChIP target, in RH4 cells treated with either DMSO or Entinostat (top), compared with AQuA-HiChIP using exogenous reference chromatin spike-in (bottom), at the MYOD1 super enhancer containing locus. b, SE-to-SE contact loss, amidst aberrant SE-contact spreading at SOX8 cis-regulatory elements. Top, AQuA-HiChIP contact heatmaps (DMSO, Entinostat 6 hours, in RH4 cells); bottom, virtual 4C analysis (change in AQuA-HiChIP contact frequency, with increases colored dark pink and decreases in blue) anchored at SE1 upstream or SE3 downstream of SOX8. c, Hyper-acetylation causes expansive gains of aberrant SE contacts, shown by AQuA-HiChIP of H3K27ac in RH4 cells, treated for 6 hours with DMSO (top row) or Entinostat (bottom row), visualized at 7 core regulatory domains. Super enhancers are indicated by red bars above the contact frequency heatmaps. CR TF genes are shown in dark blue.