DIFFERENTIAL REGULATION OF AP-1 AND NOVEL TRE-SPECIFIC DNA-BINDING COMPLEXES DURING DIFFERENTIATION OF OLIGODENDROCYTE-TYPE-2-ASTROCYTE (O-2A) PROGENITOR CELLS

AP-1 is an ubiquitous transcription factor which is composed of the Ju n and Fos proto-oncogene proteins and is thought to play a role in bot h cell proliferation and differentiation, We have used an immortal, bi potential oligodendrocyte-type-2 astrocyte progenitor cell line (O-2A/ c-myc) which can differentiate into oligodendrocytes or type-2 astrocy tes in vitro, to investigate whether AP-1 DNA-binding activity fluctua tes during glial cell differentiation, Unexpectedly, DNA-mobility shif t assays using a TRE-containing oligonucleotide derived from the promo ter of the glial-specific gene, glial fibrillary acidic protein (GFAP/ AP-1), revealed that O-2A/c-myc progenitor cells were devoid of conven tional AP-1 DNA-binding complexes, O-2A/c-myc cells did however contai n several novel GFAP/AP-1-specific DNA-binding complexes, which we hav e termed AP(prog). AP(prog) complexes recognise the TRE consensus moti f present in the GFAP/AP-1 oligonucleotide together with adjacent 3' s equences but do not contain c-Jun or any other known Jun-related prote ins, When O-2A/c-myc cells underwent terminal differentiation AP(prog) complexes were lost and conventional AP-1 DNA-binding activity became evident, particularly in astrocytes. These changes appear to be close ly linked to the differentiation process since they did not occur in a derivative of the O-2A/c-myc cell line that contains an activated v-r as oncogene and which fails to differentiate under appropriate culture conditions, The inverse regulation of conventional AP-1 and AP(prog) complexes within the O-2A lineage suggests that these factors may play a role in the regulation of glial cell differentiation or glial cell- specific gene expression.