Brn-5 is a divergent POU domain factor highly expressed in layer IV of the neocortex

We have identified rat cDNA clones that encode a POU domain protein, referred to as brain-5 (Brn-5). During embryogenesis in the rat, Brn-5 is widely expressed with highest levels in the developing brain and spinal cord from embryonic day 12.5. In the adult, Brn-5 mRNA is most abundant in the brain, where it is diffusely expressed with the exception of an enrichment in layer IV of the neocortex. However, Brn-5 is also found in multiple adult tissues outside the central nervous system, including kidney, lung, heart, adrenal, skin, testis, and anterior pituitary. This expression pattern contrasts with that of most other POU domain genes that are expressed predominantly in the developing nervous system and are progressively restricted to discrete regions of the brain. The predicted amino acid sequence of Brn-5 is considerably divergent from previously described POU domains and thus defines a new POU domain subclass (class VI). Consistent with its divergent sequence, the DNA-binding characteristics of Brn-5 overlap with, but are clearly distinct from, that of Oct-2. Although Brn-5 can bind to non-octamer sites, a random site selection indicates that its preferred binding site contains a variant octamer core motif. Finally, we show that the amino terminus of Brn-5 contains a transactivation domain.