EXPRESSION OF MULTIPLE CLASSES OF THE NUCLEAR FACTOR-I FAMILY IN THE DEVELOPING HUMAN BRAIN - DIFFERENTIAL EXPRESSION OF 2 CLASSES OF NF-1 GENES

Nuclear factor-1 (NF-1) is a multifunctional protein that participates in both transcription and replication. NF-1 proteins exist as a famil y of proteins that share some common structural and functional feature s but also demonstrate organ and cell type specific expression. Based upon these characteristics, the family of NF-1 proteins is divided int o four classes, A, B, C and D. Several NF-1 binding sites have been id entified in the regulatory sequences of the human polyomavirus, JCV, w hich multiplies most efficiently in glial cells derived from human fet al brain. Nuclear proteins from these cultures bind specifically to th ese NF-1 sites. It is not known, however, which member(s) of the NF-1 family is expressed in cells susceptible to JCV infection. We have exa mined glial cells as well as HeLa cells, which are not permissive to J CV, for NF-1 expression. By RT-PCR analysis, ail four classes of NF-1 are expressed in human fetal glial cells and HeLa cells. However, by N orthern analysis the expression of class D gene is much higher in the glial cells than HeLa cells. Expression of the class C gene, first ide ntified in HeLa cells as NF-1/CTF1, is barely detectable in glial cell s but highly expressed in HeLa cells. The screening of cDNA libraries from two early human brain tissues resulted in the identification of a number of clones which appear to be related and belong to a single cl ass of the NF-1 family, class D. Nucleotide sequence of one clone, des ignated NF-1/AT1, confirms this. The NF-1/AT1 protein was overexpresse d in E coli and found tl, bind specifically to an NF-1 probe by gel sh ift analysis. Southern analysis of human fetal glial cells indicates t hat the NF-1/AT1 gene, class D, is derived from a different gene than NF-1/CTF1. These results suggest the possibility that genes or viruses , like JCV, which use NF-1 for their expression in human brain derived cells may preferentially use the NF-1 class D protein.