Expression of the aldehyde dehydrogenase 2-like gene is controlled by BOB.1/OBF.1 in B lymphocytes.
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 gamma, alpha-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.
Brunner
Cornelia
C
University of Ulm, Department of Physiological Chemistry, Albert-Einstein-Allee 11, D-89081 Ulm, Germany.
Laumen
Helmut
H
Nielsen
Peter J
PJ
Kraut
Norbert
N
Wirth
Thomas
T
D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D020816:Amino Acid Motifs; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D015536:Down-Regulation; D005838:Genotype; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
D002843:Chromatin; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; C091546:POU2AF1 protein, human; C490424:Pou2af1 protein, mouse; C491013:SLC22A2 protein, human; C491012:Slc22a2 protein, mouse; D015534:Trans-Activators; D012313:RNA; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial