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J. Biol. Chem., Vol. 278, Issue 46, 45231-45239, November 14, 2003

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Expression of the Aldehyde Dehydrogenase 2-like Gene Is Controlled by BOB.1/OBF.1 in B Lymphocytes^*

Cornelia Brunner, Helmut Laumen, Peter J. Nielsen, Norbert Kraut¶||, and Thomas Wirth**

From the University of Ulm, Department of Physiological Chemistry, Albert-Einstein-Allee 11, D-89081 Ulm, Germany, Max Planck Institute for Immunology, Stübeweg, D-79108 Freiburg, Germany, and ^¶Boehringer Ingelheim Austria GmbH, R&D Vienna/Exploratory Research, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria

BOB.1/OBF.1 is a lymphocyte-restricted transcriptional coactivator. It binds to the Oct1 and Oct2 transcription factors and increases their transactivation potential. Targeted gene disruption experiments revealed that BOB.1/OBF.1 is critical at different stages of B cell development. A large number of genes expressed in B cells contain octamer motifs in their regulatory regions. However, only few genes have been described so far whose expression is dependent on BOB.1/OBF.1. To understand the molecular basis of BOB.1/OBF.1 function in B cell development, we searched for BOB.1/OBF.1 target genes by expression profiling. We have identified genes both induced and repressed by BOB.1/OBF.1. Using different genetic systems, we demonstrate regulation of a selection of these genes. Identified targets included genes encoding Ahd2-like, AKR1C13, Rbp1, Sdh, Idh2, protocadherin , -catenin, Ptprs, Id3, and Creg. Classification of BOB.1/OBF.1 target genes by function suggests that they affect various aspects of B cell physiology such as cellular metabolism, cell adhesion, and differentiation. To better understand the mechanism of BOB.1/OBF.1 action, we cloned the promoter of the gene encoding Ahd2-like, the gene showing the strongest regulation by BOB.1/OBF.1. This promoter indeed contains a perfect octamer motif. Furthermore, the motif was recognized by the Oct transcription factors as well as BOB.1/OBF.1 in vitro and in vivo, as shown by electromobility shift and chromatin immunoprecipitation assays. Transient transfections confirm that this promoter is activated by BOB.1/OBF.1. Our observations suggest that by regulating genes in different functional pathways, BOB.1/OBF.1 has a widespread effect on B cell development and function.

Received for publication, March 12, 2003 , and in revised form, August 1, 2003.

^* This work was supported by Deutsche Forschungsgemeinschaft Grant DFG SFB 497, C5 (to T. W.) and by the Fonds der Chemischen Industrie. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence may be addressed. Tel.: 43-1-80105-2783; Fax: 43-1-80105-2782; E-mail: norbert.kraut{at}vie.boehringer-ingelheim.com.

^** To whom correspondence may be addressed. Tel.: 49-731-501-3270; Fax: 49-731-502-2892; E-mail: thomas.wirth{at}medizin.uni.ulm.de.

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