REGULATION OF IMMUNOGLOBULIN GENE-TRANSCRIPTION

This chapter examines regulation of immunoglobulin gene transcription. It provides an overview of cis-acting DNA sequence elements and the trans-acting factors that interact with them, with emphasis on factors that are likely to be critical in the stage-specific activation of the immunoglobulin genes. Promoters required for transcription of immunoglobulin genes are located 5′ of all variable region gene segments and can be brought into the proximity of the constant region-associated enhancers by recombination. The most striking feature of immunoglobulin promoters is the presence of a conserved octanucleotide motif. Deletion of this site in the heavy chain promoter results not only in loss of promoter activity in transient transfection assays, but in complete loss of lymphoid expression of a heavy chain transgene in mice. The analysis of the immunoglobulin gene suggests that their expression is controlled through the combinatorial action of tissue- and stage-specific factors (OTF-2, TF-μB) and more widely expressed E motif-binding factors such as E47/E12. An additional level of regulation is imparted by combinatorial mechanisms such as adjacent DNA-binding elements and factors that may alter activity and “cofactors” that, by forming a complex with the bound factor, affect its activation of a gene in a particular cell type. © 1992 Academic Press Inc.