Abstract
Although enhancers activate transcription from long distances, they stimulate transcription only through short-range interactions with the RNA polymerase II machinery. I posit that action at a distance is mediated by loops between distal and proximal enhancers that thereby bring proteins associated with distal enhancers near promoters. This Comment posits that enhancers stimulate the transcription machinery only through short-range interactions and, therefore, that enhancer activity at a distance is mediated by chromatin loops between distal and proximal enhancers, not between enhancers and promoters.