The BOB.1 / OBF.1 co-activator is essential for octamer-dependent transcription in B cells.
The BOB.1 / OBF.1 / OCA-B protein (henceforth designated as BOB.1 / OBF.1) is a B cell-specific co-activator of the Oct1 and Oct2 transcription factors. It is involved in mediating the transcriptional activity of these proteins. Surprisingly, animals deficient for BOB.1 / OBF.1 showed normal expression of genes that contain an octamer motif in their regulatory regions. Here we have addressed the role of BOB.1 / OBF.1 for octamer-dependent transcription. We show that promoters exclusively dependent on functional octamer motifs are completely inactive in BOB.1 / OBF. 1-deficient B cells. The lack of activity is a direct consequence of lack of the co-activator. To show this, a hormone-regulated conditional allele of BOB.1 / OBF.1 was introduced into the BOB.1 / OBF.1-deficient B cells. This resulted in the hormone-dependent transcriptional activity of octamer-dependent reporters in these cells. The BOB.1 / OBF.1 requirement for octamer promoter function was also observed when an authentic immunoglobulin kappa-promoter was assayed. BOB.1 / OBF.1 dependence could not be overcome by including the strong enhancer element from the immunoglobulin heavy chain gene. Induction of pre-B cells with lipopolysaccharide led to increased Oct2 levels but did not significantly increase octamer-dependent transcription in BOB.1 / OBF.1-deficient B cells. Thus, these results demonstrate that BOB.1 / OBF.1 itself is a non-redundant protein in B cells and absolutely required for octamer-dependent transcriptional activity.
Laumen
H
H
Institut für Medizinische Strahlenkunde und Zellforschung Universität Würzburg, Würzburg, Germany.
Nielsen
P J
PJ
Wirth
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology
C490424:Pou2af1 protein, mouse; D015534:Trans-Activators