CELL-TYPE-SPECIFIC TRANSCRIPTIONAL ACTIVATION AND SUPPRESSION OF THE ALPHA(1B) ADRENERGIC-RECEPTOR GENE MIDDLE PROMOTER BY NUCLEAR-FACTOR-1

Nuclear factor 1 (NF1) has been reported to be a transcriptional activ ator for some genes and a transcriptional silencer for others, Here we report that in Hep3B cells, cotransfection of NF1/L, NF1/Red1, or NF1 /X with the alpha(1B) adrenergic receptor (alpha(1B)AR) gene middle (P 2) promoter increases P2 activity to more or less the same degree, whe reas in DDT1 MF-2 cells cotransfection of NF1/L or NF1/Red1 causes a s mall but statistically significant decrease in the P2 promoter activit y, and NF1/X causes a greater, 70% inhibition. Further experiments usi ng truncated NF1/X mutants indicate that NF1/X contains both positive and negative regulatory domains. The positive domain, located between amino acids 416 and 505, is active in Hep3B cells, whereas the negativ e domain, located between amino acids 243 and 416, is active in DDT1 M F-2 cells, These functional domains are also capable of regulating tra nscription when isolated from their natural context and fused into the GAL4 binding domain. Furthermore, NF1 affinity purified from rat live r nuclear extracts copurified with a non-DNA binding protein, which ca n bind to the P2 promoter of the alpha(1B)AR gene via interacting with NF1, Taken together, these findings indicate that NF1/X contains both activation and suppression domains that may be recognized and modulat ed by cell type-specific cofactors, This may be one of the mechanisms whereby NF1 can activate or suppress the expression of different genes , and it may also underlie the tissue-specific regulation of the alpha (1B) AR gene.