AI Article Synopsis
- The study investigates the regulatory mechanisms behind the transcription of the human choline acetyltransferase (hChAT) gene, focusing on the roles of c-Myb and C/EBPbeta in transactivation.
- It finds that both transcription factors can independently activate promoter P2 of the hChAT gene, with their simultaneous expression resulting in a significantly higher activation synergistically enhanced by the coactivators CBP/p300.
- The research highlights the presence of a composite element that includes binding sites for both c-Myb and C/EBPbeta, indicating a similar synergistic function in neuronal systems as observed in hematopoietic cells.
Article Abstract
To elucidate regulatory mechanisms at the transcriptional level of the human choline acetyltransferase gene (hChAT) we performed cotransfections assays in NG108-15 and SN56 cells using ChAT-CAT reporter plasmids with c-Myb and C/EBPbeta expression plasmids. The hChAT gene has several promoters, one of which (promoter P2 or M-type) is both c-Myb and C/EBPbeta inducible as 3-4-fold trans-activation was obtained in both cell lines when using either c-Myb or C/EBPbeta expression vectors alone. The simultaneous expression of c-Myb and C/EBPbeta in the absence or presence of NGFI-C (egr4) leads respectively to a 15-fold and 32-fold synergistic transcriptional activation of promoter P2. In the region upstream of exon M (P2) we identified a functional composite element including a c-Myb next to a C/EBP binding site. An oligonucleotide containing the composite element confers c-Myb and C/EBPbeta responsiveness to a heterologous promoter which is reduced after mutation of the c-Myb binding site. We also show that the coactivators CBP/p300 are required for c-Myb and C/EBPbeta trans-activation function and that RARalpha, RXRalpha and T3R have an inhibitory action on the synergistic transcriptional activity of c-Myb and C/EBPbeta and propose a model to explain the phenomena. Taken together, the results suggest that the synergistic effect of c-Myb and C/EBPbeta, previously observed in the hematopoietic system, functions equally in the neuronal system.
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| http://dx.doi.org/10.1016/s0169-328x(02)00419-9 | DOI Listing |
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