THE CEREBELLUM-ENRICHED FORM OF NUCLEAR FACTOR-I IS FUNCTIONALLY DIFFERENT FROM UBIQUITOUS NUCLEAR FACTOR-I IN GLIAL-SPECIFIC PROMOTER REGULATION

Nuclear factor I (NFI) binding sites are present in a wide range of br ain-specific gene enhancer and promoter sequences and appear to play a role in establishing cell type-specific expression within the CNS. Th e precise mechanisms used by various members of the NFI family of prot eins to confer brain-specific expression are unclear. We have addresse d this issue by comparing the transactivating capabilities of two form s of NFI in directing gliotropic expression from two different JC viru s (JCV) promoter configurations. The JCV is an opportunistic pathogen of humans that causes lytic destruction of the oligodendrocytes and th us demyelination in immunocompromised patients. Our results show that the cerebellum-enriched form of NFI (NFI-A1) transactivates two gliotr opic JCV early promoters to a greater extent than the ubiquitous form of NFI (NFI-C1), Activation by NFI-A1 was dramatically greater in glia l than in nonglial cells. These results suggest that NFI proteins dire ct brain-specific expression through combinatorial interactions with c ell specific coactivators and/or transcription factors that recognize adjacent sites within brain specific promoters.