The dual effects of the astrocyte-specific enhancer of the AQP4 M1 promoter.

Aquaporin-4, a predominant water channel in the central nervous system, has two isoforms, M1 and M23, whose transcripts are driven by distinct promoters. Using a reporter assay, we found that a fragment located between exons 0 and 1 of the mouse aquaporin-4 gene, which had been thought to be the promoter for M23, lacked enhancers functioning in astrocytes. When the astrocyte-specific enhancer (ASE) of the M1 promoter is connected to the putative M23 core promoter, it also works in astrocytes. Importantly, the ASE inhibits downstream promoter activity in NIH3T3 cells, indicating that the ASE also functions as a silencer in cells lacking aquaporin-4.