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Publication : Autoregulatory sequences are revealed by complex stability screening of the mouse brn-3.0 locus.

First Author  Trieu M Year  1999
Journal  J Neurosci Volume  19
Issue  15 Pages  6549-58
PubMed ID  10414983 Mgi Jnum  J:56447
Mgi Id  MGI:1340968 Doi  10.1523/JNEUROSCI.19-15-06549.1999
Citation  Trieu M, et al. (1999) Autoregulatory sequences are revealed by complex stability screening of the mouse brn-3.0 locus. J Neurosci 19(15):6549-58
abstractText  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 mouse brn-3.0 locus. This method is based on the observation that the kinetic stability of Brn3.0 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 similar to 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.
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