Redundancy of Class III POU Proteins in the Oligodendrocyte Lineage*
- Jörg Schreiber‡,
- Janna Enderich‡,
- Elisabeth Sock‡,
- Claudia Schmidt‡,
- Christiane Richter-Landsberg§ and
- Michael Wegner‡¶
- From the ‡Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany and the §Department of Biology, Universität Oldenburg, D-26111 Oldenburg, Germany
Abstract
Class III POU proteins are prominent regulators of neural development. Tst-1/Oct6/SCIP, for instance, is essential for terminal differentiation of myelinating Schwann cells in the peripheral nervous system. Although Tst-1/Oct6/SCIP is also expressed in the myelin forming oligodendrocytes of the central nervous system, targeted deletion of Tst-1/Oct6/SCIP failed to reveal a gross alteration of myelination in the central nervous system. To better understand this apparent discrepancy, we examined the expression of POU proteins in both cultured primary oligodendrocytes and in the oligodendrocyte-like CG-4 cell line. These cells expressed Tst-1/Oct6/SCIP, Brn-1, and Brn-2 in significant amounts, indicating that Brn-1 and Brn-2 might have the capacity to compensate loss of Tst-1/Oct6/SCIP. We show that Tst-1/Oct6/SCIP, Brn-1, and Brn-2 were all down-regulated during the early phases of oligodendrocyte development both on RNA and protein level. All three POU proteins exhibited similar DNA binding characteristics. When promoters consisting of a single POU protein-binding site adjacent to a TATA box were used as reporters in transient transfections, Brn-1 proved to be a weaker transcriptional activator than Tst-1/Oct6/SCIP. In agreement with this, we found the transactivation domain of Brn-1, which we mapped between amino acids 119 and 237, significantly weaker than the transactivation domain of Tst-1/Oct6/SCIP. Taken together, our data imply a partial, but not complete redundancy between POU proteins in oligodendrocytes.
Footnotes
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↵* This work was supported by Deutsche Forschungsgemeinschaft Grant We 1326/5-2 (to M. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed: ZMNH, Martinistr. 52, D-20246 Hamburg, Germany. Tel.: 49-40-4717-6274; Fax: 49-40-4717-6602; E-mail: wegner{at}plexus.uke.uni-hamburg.de.
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↵1 The abbreviations used are: bp, base pair(s); RT-PCR, reverse transcriptase-polymerase chain reaction; kb, kilobase(s); DBD, DNA-binding domain; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; CMV, cytomegalovirus.
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↵2 K. Kuhlbrodt and M. Wegner, manuscript in preparation.
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- Received June 27, 1997.
- Revision received October 10, 1997.
