PT - JOURNAL ARTICLE AU - May Trieu AU - Jerry M. Rhee AU - Natalia Fedtsova AU - Eric E. Turner TI - Autoregulatory Sequences are Revealed by Complex Stability Screening of the Mouse <em>brn-3.0</em> Locus AID - 10.1523/JNEUROSCI.19-15-06549.1999 DP - 1999 Aug 01 TA - The Journal of Neuroscience PG - 6549--6558 VI - 19 IP - 15 4099 - http://www.jneurosci.org/content/19/15/6549.short 4100 - http://www.jneurosci.org/content/19/15/6549.full SO - J. Neurosci.1999 Aug 01; 19 AB - The POU-IV or Brn-3 class of transcription factors exhibit conserved structure, DNA-binding properties, and expression in specific subclasses of neurons across widely diverged species. In the mouse CNS, Brn-3.0 expression characterizes specific neurons from neurogenesis through the life of the cell. This irreversible activation of expression suggests positive autoregulation. To search for cis-acting elements that could mediate autoregulation we used a novel method, complex stability screening, which we applied to rapidly identify functional Brn-3.0 recognition sites within a large genomic region encompassing the mousebrn-3.0 locus. This method is based on the observation that the kinetic stability of Brn-3.0 complexes with specific DNA sequences, as measured by their dissociation half-lives, is highly correlated with the ability of those sequences to mediate transcriptional activation by Brn-3.0. The principal Brn-3.0 autoregulatory region lies ∼5 kb upstream from the Brn-3.0 transcription start site and contains multiple Brn-3.0-binding sites that strongly resemble the optimal binding site for this protein class. This region also mediates transactivation by the closely related protein Brn-3.2, suggesting a regulatory cascade of POU proteins in specific neurons in which Brn-3.2 expression precedes Brn-3.0.