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International Immunology, Vol. 11, No. 5, 813-824, May 1999
© 1999 Japanese Society for Immunology

Differential regulation of transcription termination occurring at two different sites on the µ–{delta} gene complex

Myoung Kim, Ping Qiu, Raed Abuodeh, Jianzhu Chen1 and Dorothy Yuan

Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
1 Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA

Correspondence to: D. Yuan

The progression of polymerases across the µ–{delta} Ig heavy chain gene complex is characterized by two termination events occurring at different sites on the transcription unit and at different times during B cell differentiation. We have utilized two mouse strains to analyze the regulatory determinants for these events in primary B cells. In the transgenic pµ.µ{delta}Ratt strain a 1160 bp intervening DNA segment (the att site) has been inverted. This mutation results in the abrogation of transcription termination that occurs in early B cells. Using a novel method that takes advantage of an internal ribosome entry site we have further restricted the size of the segment that is needed for inducing transcription termination in transfectants. This 200 bp termination-inducing sequence operates in tumor equivalents of early but not mature B cells and the activity is correlated with differential binding of nuclear proteins. To explore the regulatory basis for the change in site of transcription termination upon B cell activation we have examined the µS–/– deletion mutant strain in which the µS poly(A) site has been eliminated. The results suggest that polyadenylation at the µS site plays a dominant but not exclusive role in regulating transcription termination in activated B cells.

Keywords: B lymphocytes, transcription termination, polyadenylation, IgD, IgM, internal ribosome entry site

Transmitting editor: K. Knight


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