YY1 Binding to Regulatory Elements that Lack Enhancer Activity Promotes Locus Folding and Gene Activation

Enhancers activate their cognate promoters over huge distances but how enhancer/promoter interactions become established is not completely understood. There is strong evidence that cohesin-mediated loop extrusion is involved but this does not appear to be a universal mechanism. Here, we identify an element within the mouse immunoglobulin lambda (Ig{lambda}) light chain locus, HSC{lambda}1, that has characteristics of active regulatory elements but lacks intrinsic enhancer or promoter activity. Remarkably, knock-out of the YY1 binding site from HSC{lambda}1 reduces Ig{lambda} transcription significantly and disrupts enhancer/promoter interactions, even though these elements are >10 kb from HSC{lambda}1. Genome-wide analyses of mouse embryonic stem cells identified 3503 similar YY1-bound, putative genome organizing elements that lie within CTCF/cohesin loop boundaries but that lack intrinsic enhancer activity. We suggest that such elements play a fundamental role in locus folding and in facilitating enhancer/promoter interactions. HighlightsHow long-range enhancer-promoter interactions are established is not fully understood An element in the lambda light chain locus, HSC{lambda}1, lacks intrinsic enhancer activity Removal of YY1 binding from HSC{lambda}1 disrupts neighbouring enhancer/promoter contacts Genome-wide analyses detect similar elements that lack enhancer or promoter activity We propose these elements aid locus folding and nearby enhancer-promoter interactions O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=64 SRC="FIGDIR/small/554459v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@562875org.highwire.dtl.DTLVardef@7a1a85org.highwire.dtl.DTLVardef@634652org.highwire.dtl.DTLVardef@19ddfda_HPS_FORMAT_FIGEXP M_FIG C_FIG