Stable propagation of the active transcriptional state of an immunoglobulin mu gene requires continuous enhancer function

Abstract

Enhancer sequences control the expression of the immunoglobulin mu heavy chain gene. In this study we examined whether the active transcriptional state of the mu gene can be propagated from mother to daughter cells after deletion of its enhancer. A mu gene that contains the enhancer flanked by D and J recombination signals was stably introduced into pre-B cells, resulting in mu gene transcription. Subsequent deletion of the enhancer from the transfected gene by D-to-J joining reproducibly resulted in switching off of mu expression. Moreover, transcriptional inactivation occurred although the mu gene was found to be hypomethylated prior to deletion of the enhancer. We conclude that the enhancer does not confer upon the mu gene "memory" of its active transcriptional state. Thus, the enhancer seems to be required both for establishment and for maintenance of mu gene expression.