A 5' BETA-GLOBIN MATRIX-ATTACHMENT REGION AND THE POLYOMA ENHANCER TOGETHER CONFER POSITION-INDEPENDENT TRANSCRIPTION

Insertions of reporter constructs into the genome of higher eukaryotes typically lead to variegated gene expression due to position effects at the sites of integration. The 20-kb human beta-globin (beta Glb) lo cus control region (LCR)has been found to dampen these position effect s when included in an expression vector. Several studies have indicate d that much of the activity of the beta Glb-LCR resides in hypersensit ive site II, which contains a strong enhancer. In this study, we have focused on the matrix-attachment region (MAR) at the 5' boundary of th e beta Glb-LCR. We find that the beta Glb-MAR, by itself, has little e ffect on transcription of a reporter gene in stable transformants. How ever, when the beta Glb-MAR is linked in cis with the polyoma virus en hancer, the MAR-enhancer construct confers high levels of copy-depende nt transcription that is independent of the chromosomal site of integr ation. These results suggest that the beta Glb-MAR may work synergisti cally with particular enhancer elements to dampen chromosomal position effects and ensure high-level expression.