The Octamer/μE4 Region of the Immunoglobulin Heavy-Chain Enhancer Mediates Gene Repression in Myeloma × T-Lymphoma Hybrids

Abstract

We have shown previously that the immunoglobulin heavy-chain enhancer acts as a repressor of gene transcription in hybrids between immunoglobulin-producing myelomas and a T-lymphoma line. We have now mapped this repressive activity to a 51-bp enhancer subfragment which contains the octamer and mu E4 protein-binding motifs. Even a single copy of this subfragment will repress gene expression in hybrid cells. Mutational analyses of the repressor fragment suggest that in non-B cells, a strong transcriptional repressor(s) functions through the same motifs important for gene activation in B cells. Changes in chromatin structure that accompany reporter gene repression suggest a general mechanism for prohibiting immunoglobulin heavy-chain locus activation in inappropriate cell types.