REDUNDANCY OF CLASS-III POU PROTEINS IN THE OLIGODENDROCYTE LINEAGE

Class III POU proteins are prominent regulators of neural development. Tst-1/Oct6/SCIP, for instance, is essential for terminal differentiat ion of myelinating Schwann cells in the peripheral nervous system. Alt hough Tst-1/Oct6/SCIP is also expressed in the myelin forming oligoden drocytes of the central nervous system, targeted deletion of Tst-1/Oct 6/SCIP failed to reveal a gross alteration of myelination in the centr al nervous system. To better understand this apparent discrepancy, we examined the expression of POU proteins in both cultured primary oligo dendrocytes and in the oligodendrocyte-like CG-4 cell line. These cell s expressed Tst-1/Oct6/SCIP, Bm-l, and Brn-2 in significant amounts, i ndicating that Bm-l and Brn-2 might have the capacity to compensate lo ss of Tst-1/Oct6/SCIP, We show that Tst-1/Oct6/SCIP, Bm-l, and Brn-2 w ere all down-regulated during the early phases of oligodendrocyte deve lopment both on RNA and protein level. All three POU proteins exhibite d similar DNA binding characteristics. When promoters consisting of a single POU protein-binding site adjacent to a TATA box were used as re porters in transient transfections, Bm-l proved to be a weaker transcr iptional activator than Tst-1/Oct6/SCIP. In agreement with this, we fo und the transactivation domain of Bm-l, which we mapped between amino acids 119 and 237, significantly weaker than the transactivation domai n of Tst-1/Oct6/SCIP. Taken together, our data imply a partial, but no t complete redundancy between POU proteins in oligodendrocytes.