Alternative splicing of the Oct-2 transcription factor RNA is differentially regulated in neuronal cells and B cells and results in protein isoforms with opposite effects on the activity of octamer/TAATGARAT-containing promoters.
The RNA encoding the octamer-binding transcription factor Oct-2 is alternatively spliced in both neuronal cells and in B cells to yield multiple mRNAs encoding different isoforms of the protein. We show that, compared with B cells, neuronal cells overexpress the mRNAs encoding Oct 2.4 and 2.5 which differ from the other forms (Oct 2.1, 2.2, and 2.3) at the C terminus of the protein. When introduced into cells lacking endogenous Oct-2, the various Oct-2 isoforms have different effects on octamer-containing promoters. The Oct 2.1, 2.2, and 2.3 forms stimulate all octamer-containing promoters. However, the Oct 2.4 and 2.5 forms can repress some promoters and stimulate others, depending on the sequence of the octamer motif and its context within the promoter. In contrast, when introduced into neuronal cells which express a high endogenous level of the inhibitory Oct 2.4 and 2.5 forms, all the Oct-2 isoforms can repress octamer-mediated gene expression. The significance of these findings is discussed with regard to the known inhibitory effect of the octamer motif on viral and cellular gene expression in neuronal cells.
D017398:Alternative Splicing; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D001921:Brain / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000502:physiology*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000502:physiology*; D050813:Octamer Transcription Factor-2; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics* / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012689:Sequence Homology, Nucleic Acid; D018139:Simplexvirus / Q000235:genetics; D013154:Spleen / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D050813:Octamer Transcription Factor-2; C489205:Pou2f2 protein, rat; D014157:Transcription Factors; D012313:RNA