Role of the intronic elements in the endogenous immunoglobulin heavy chainlocus - Either the matrix attachment regions or the core enhancer is sufficient to maintain expression

High level expression in mice of transgenes derived from the immunoglobulin heavy chain (IgH) locus requires both the core enhancer (E mu) and the mat rix attachment regions (MARs) that flank E mu. The need for both elements i mplies that they each perform a different function in transcription. While it is generally assumed that expression of the endogenous IgH locus has sim ilar requirements, it has been difficult to assess the role of these elemen ts in expression of the endogenous heavy chain gene, because B cell develop ment and IgH expression are strongly interdependent and also because the lo cus contains other redundant activating elements. We have previously descri bed a gene-targeting approach in hybridoma cells that overcomes the redunda ncy problem to yield a stable cell line in which expression of the IgH locu s depends strongly on elements in the MAR-E mu-MAR segment. Using this syst em, we have found that expression of the endogenous mu gene persists at sub stantially (similar to 50%) normal levels in recombinants which retain eith er the MARs or E mu. That is, despite the dissimilar biochemical activities of these two elements, either one is sufficient to maintain high level exp ression of the endogenous locus. These findings suggest new models for how the enhancer and MARs might collaborate in the initiation or maintenance of transcription.