I have been doing ChIP experiments on brain tissues as well as immortalized cell lines (I use Diagenode's auto Chip kit). I see good enrichment for histone modifications and Pol II at promoters of my interest and very little background signal from my IgG control. However, I also see a substantial amount of signal from a desert intergenic region as well as other gene bodies (devoid of histone marks or Pol II binding site). Additional sonication steps could not help much.
Did anyone have a similar experience? Could tiering down antibody level solve the issue?
thanks a lot for your help.