A nuclear DNA attachment element mediates elevated and position-independent gene activity

Abstract

The transcriptional activity of genes that have randomly integrated into the genomes of transfected cells and transgenic organisms is in general unpredictable, varying with the chromosomal site of the insertion. This effect of chromosomal position on gene expression may reflect the organization of chromosomes into topologically constrained loops and functional domains. To assess the biological significance of these loop domains, the anchorage of DNA to the nuclear scaffold has been studied at specific gene loci. We have previously defined cis-acting regions flanking the chicken lysozyme-gene domain that mediate the attachment of the chromatin to the nuclear scaffold. These 'A-elements' map to the 5' and 3' boundaries of the region of general DNase sensitivity in the active chromatin, which contains the lysozyme gene and its cis-regulatory elements. Here we report that when a reporter gene is flanked by 5' A-elements from the lysozyme gene, its expression in stably transfected cells is significantly elevated and is independent of chromosomal position.