NF-KAPPA-B-LIKE FACTORS IN THE MURINE BRAIN - DEVELOPMENTALLY-REGULATED AND TISSUE-SPECIFIC EXPRESSION

NF-kappaB and related factors are important transducers of external si gnals to the cell nucleus. They are abundant in the brain, where they may be significant for the regulation of gene transcription in plastic ity-related processes for instance, via activation of protein kinase C . The subunit composition and levels of these factors in the mouse and rat brain and other tissues, using an assay based on get retardation of the oligonucleotides corresponding to the kappaB DNA-element, are r eported here. Three major kappaB-binding factors were observed. Factor s I and II were activated by the dissociating agent deoxycholate. DNA protein cross-linking and antibody neutralization experiments suggest that factor I is a heterodimer of c-Rel and p65; factor II is a hetero dimer of p50 and p65 (authentic NF-kappaB), and of p50 and c-Rel; fact or III is the p50 homodimer (KBF1). All three factors were generally e xpressed in the 17-day-old rat embryo and 5-day-old pup, whereas in th e adult rat, expression was more limited and showed certain tissue spe cificity. Factor II was the most generally expressed and the only fact or observed in adult brain. Factor I was only detected in the adult te stis whereas factor III was observed in the adult spleen and, in small amounts, in the liver and lung. Two minor kappaB-specific factors (A and B), distinctive to the brain and spleen, respectively, showed very slow gel mobility. Their estimated molecular weights were about 125 k Da and 95 kDa, respectively. Expression of factor A was stable in the rat brain during development. Factor A may be identical to a previousl y described brain-specific factor, BETA (Korner et al., Neuron, 3 (198 9) 563-572). Thus, the expression pattern of kappaB-binding activities is apparently developmentally regulated and tissue-specific particula rly in the adult. In the adult mouse and rat brain, only factors II (p robably NF-kappaB and p50/c-Rel heterodimer) and A (probably BETA) cou ld be observed.