title: Promoters with the octamer DNA motif (ATGCAAAT) can be ubiquitous or cell type-specific depending on binding affinity of the octamer site and Oct-factor concentration.
abstract: Immunoglobulin (Ig) gene promoters contain the octamer sequence motif ATGCAAAT which is recognized by cellular transcription factors (Oct factors). Besides the ubiquitous Oct-1 factor, there is also a group of related factors (Oct-2 factors) encoded by a separate gene. The Oct-2 gene is regulated in a cell-type specific manner, and the protein is present in large amounts in B lymphocytes. We have previously shown that simple composite promoters of an octamer/TATA box type are poorly active in non-B cells but are strongly responsive to ectopic expression of Oct-2A factor, a major representative of the lymphocyte Oct-2 factors. In the present study we have tested the activity of a number of composite promoters and natural Ig promoters, and their response to Oct-1 and Oct-2 factors. Unexpectedly, we find that octamer/TATA promoters with a high affinity octamer site direct ubiquitous expression. By contrast, promoter constructions that behave in a B cell-specific manner tend to have a weak octamer binding site. These promoters are responsive to ectopic expression of additional Oct-factor, irrespective of whether it is Oct-1 or Oct-2. Using natural Ig promoters rather than composite promoters, we find that an IgH promoter is well transcribed in non-B cells via the ubiquitous Oct-1 factor, while Ig kappa and Ig lambda light chain promoters require additional Oct factor for maximal expression. It seems therefore likely that during B cell differentiation, Ig heavy chain promoters can be activated by Oct-1, before the appearance of Oct-2 factors. Oct-2 factors then would serve to boost the expression from Ig light chain promoters, which are known to be activated only after successful heavy chain gene rearrangement.
authors.affiliation: Institut für Molekularbiologie II, Universität Zürich, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Kemler
authors.forename: E
authors.initials: E
authors.lastname: Bucher
authors.forename: K
authors.initials: K
authors.lastname: Seipel
authors.forename: M M
authors.initials: MM
authors.lastname: Müller-Immerglück
authors.forename: W
authors.initials: W
authors.lastname: Schaffner
mesh_terms: D001345:Autoradiography; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D051863:Host Cell Factor C1; D007136:Immunoglobulins / Q000235:genetics; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D010957:Plasmids; D011401:Promoter Regions, Genetic; D016385:TATA Box; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D051863:Host Cell Factor C1; D007136:Immunoglobulins; D050811:Octamer Transcription Factor-1; D014157:Transcription Factors; D004247:DNA