The Cerebellum-Enriched Form of Nuclear Factor I Is Functionally Different from Ubiquitous Nuclear Factor I in Glial-Specific Promoter Regulation

Abstract

Nuclear factor I (NFI) binding sites are present in a wide range of brain-specific gene enhancer and promoter sequences and appear to play a role in establishing cell type-specific expression within the CNS. The precise mechanisms used by various members of the NFI family of proteins to confer brain-specific expression are unclear. We have addressed this issue by comparing the transactivating capabilities of two forms of NFI in directing gliotropic expression from two different JC virus (JCV) promoter configurations. The JCV is an opportunistic pathogen of humans that causes lytic destruction of the oligodendrocytes and thus demyelination in immunocompromised patients. Our results show that the cerebellum-enriched form of NFI (NFI-A1) transactivates two gliotropic JCV early promoters to a greater extent than the ubiquitous form of NFI (NFI-C1). Activation by NFI-A1 was dramatically greater in glial than in nonglial cells. These results suggest that NFI proteins direct brain-specific expression through combinatorial interactions with cell specific coactivators and/or transcription factors that recognize adjacent sites within brain specific promoters.