The enhancer of the immunoglobulin heavy chain locus is flanked by presumptive chromosomal loop anchorage elements

Abstract

We have located presumptive chromosomal loop anchorage elements within the mouse heavy chain immunoglobulin locus. Analysis of 31 kilobases spanning diversity, joining, enhancer, switch, and the mu and delta constant regions reveals that only a single 1-kilobase segment exhibits specific binding to nuclear matrices. It is of particular significance that the transcriptional enhancer element resides within this matrix association region (MAR). Fine structure mapping indicates that binding is mediated by A+T-rich approximately 350-base pair segments that reside on either side of the enhancer. The MAR sequences residing 5' of the enhancer contain topoisomerase II consensus sequences like the MAR located upstream of the kappa light chain gene enhancer. The heavy chain gene MARs, however, exhibit a lower affinity for matrix association compared to the kappa gene MAR. Significantly, the juxtaposition of enhancer elements with MARs appears to be evolutionarily conserved within the immunoglobulin genes, suggesting that MARs may act as positive and/or negative regulators of enhancer function.