Neuron Specificity of the Neurofilament Light Promoter in Transgenic Mice Requires the Presence of DNA Unwinding Elements

Abstract

Three reporter genes, the chloramphenicol acetyltransferase (CAT), the lacZ, and the intronless NF-L DNA, were used to test the activity of the proximal promoter region (-292 bp) of the human neurofilament light (hNF-L) gene in transgenic mice. Surprisingly, the hNF-L/CAT construct was highly sensitive to position effect, and its expression was found at low levels in several tissues of adult transgenic mice (Beaudet, L., Charron, G., Houle, D., Tretjakoff, I. Peterson, A., and Julien, J.-P. (1992) Gene (Amst.) 116, 205-214). In contrast, the hNF-L/lacZ or the hNF-L/intronless constructs were expressed exclusively in the nervous system during embryonic development and in adult animals. The DNA sequences analysis of the different reporter genes revealed the presence of matrix attachment regions (MARs) within the 3'-untranslated regions of all three transgenes. DNA unwinding elements were found within the MARs of lacZ and hNF-L gene constructs but not in the CAT gene construct. When this element was removed from the lacZ construct, expression of the hNF-L/lacZ transgene became susceptible to position effect and was no longer tissue-specific. These results indicate that DNA unwinding elements are essential for position effect independence conferred by MARs to the hNF-L basal promoter.