Positive and negative regulatory elements in the mouse albumin enhancer

Most enhancer elements so far described are comprised of multiple DNA binding sites for proteins that act to increase the rate of transcription. In this report we show that the far upstream mouse albumin enhancer element (-10.5 to -8.5 kilobase pairs) is a composite of at least three functional regions: a negative region that suppresses an otherwise positive, liver-specific enhancer element and a third region that by itself is inactive but in conjunction with the remaining elements overrides the effect of the negative region. The protein that binds to the overriding element is C/EBP, a liver-enriched transcription factor, whereas the newly identified protein that is responsible for full liver-specific enhancer activity is found in HeLa cell and spleen extracts as well as in extracts prepared from the liver. This latter protein may therefore be an example of a widely distributed protein that because of cell-specific modification or interaction has a tissue-specific, positive action on transcription.