Activation of the -Internexin Promoter by the Brn-3a Transcription Factor Is Dependent on the N-terminal Region of the Protein

doi:10.1074/jbc.270.6.2853

Activation of the -Internexin Promoter by the Brn-3a Transcription Factor Is Dependent on the N-terminal Region of the Protein (*)

From the (1)Medical Molecular Biology Unit, Department of Molecular Pathology, University College London Medical School, The Windeyer Building, Cleveland Street, London, W1P 6DB, United Kingdom,
(2)Institut Für Molekularbiologie und Tumorforschung, Philipps Universität Marburg, Emil-Mannkopff-Strasse 2, D-35037, Marburg, Federal Republic of Germany, and
(3)Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032

^§ To whom correspondence should be addressed.

Abstract

The Brn-3a, Brn-3b, and Brn-3c proteins are closely related POU (Pit-Oct-Unc) family transcription factors which are expressed predominantly in neuronal cells. We have identified the α-internexin gene as the first reported, neuronally expressed, target gene whose promoter activity is modulated by these factors. Both the Brn-3a and Brn-3c factors can activate the α-internexin promoter while Brn-3b represses it and can prevent activation by Brn-3a. Using chimeric constructs containing different regions of Brn-3a or Brn-3b, we show that activation of the α-internexin promoter requires the N-terminal region of Brn-3a. In contrast the activation by Brn-3a but not Brn-3b of an artificial promoter containing a synthetic Brn-3 binding site can be shown using the same constructs to be dependent on the POU domain of Brn-3a. Moreover, the isolated POU domain of Brn-3a can activate this artificial promoter but not the α-internexin promoter. Hence Brn-3a contains two distinct transactivation domains, at the N terminus and within the POU domain, whose effect is dependent upon the target promoter. The relationship of gene transactivation by Brn-3a to its ability to transform primary cells which is also dependent on the N-terminal region of the protein is discussed.

Footnotes

↵* This work was supported by Action Research, the Medical Research Council and Wellbeing (to D. S. L.), by the Deutsche Forschungsgemeinschaft (SFB215, D10) and the Mildred Scheel Stiftung Fur Krebsforschung (to T. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ T. Theil and T. Möröy, submitted for publication.
↵² The abbreviations used are:

CAT

chloramphenicol acetyltransferase

CRE

cyclic AMP response element.
- Received September 2, 1994.