YY1 is a structural regulator of enhancer-promoter loops [HiChIP]

There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not depend on this structural protein. Here we show that the transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active enhancers and promoter-proximal elements in all cells examined. YY1 forms dimers that can facilitate DNA interactions. Deletion of YY1 binding sites or depletion of YY1 can disrupt enhancer-promoter looping and normal gene expression. We propose that YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control. HiChIP against H3K27ac-marked nucleosomes in mouse embryonic stem cells HiChIP against YY1 in Jurkat, HCT-116, and K562 cells