How enhancers work - juxtapositioning of DNA control elements by synergistic interaction of Mars - (review-hypothesis).

The sites of attachment of chromatin loops to the nuclear matrix (MARs) seem to harbor transcriptional enhancers, promoters and origins of replication (ORIs). According to the model proposed, the cooperative interactions among classical nuclear matrix proteins which are abundant (topoisomerase II, histone H1, HMG-I(Y), lamins A, B1, SAF-A, ARBP and others) bring together distant AT-rich classical MAR sequences causing looping of DNA. This process juxtaposes enhancers, ORIs, promoters, and other control elements that cohabit with MARs loaded with the less abundant transcription factors (TFs) facilitating productive interactions between enhancers and promoters or enhancers and core ORIs. The implications of the model in the interactions of oncoproteins with regulatory DNA elements and their integration into a chromatin and nuclear matrix environment are discussed.