Functional role of position 22 in the homeodomain of Brn-3 transcription factors.

The Brn-3a POU family transcription factor activates a number of neuronal promoters which are repressed by the closely related Brn-3b factor. Although transcriptional activation by mutant forms of Brn-3a/Brn-3b can occur with a number of different amino acids at position 22 of the POU homeodomain, an isoleucine at this position is of critical importance for transcriptional repression. In addition, this isoleucine residue can mediate an interaction with the herpes simplex virus Vmw65 regulatory protein whereas the valine found in Brn-3a cannot do so.

The role of glycosylation in autoimmune disease.

Oligosaccharide structures play a key role in the antigenicity of a number of clinically important antigens such as blood group determinants. Interest in glycobiology has increased dramatically amongst immunologists during the last few years due to the fact that oligosaccharides also play a central role in adhesion and homing events during inflammatory processes (1), comprise powerful xenotransplantation antigens (2), and may provide targets for tumor immunotherapy (3). Additionally, alterations in glycosylation are now known to occur in a number of autoimmune diseases.

The Brn-3c transcription factor contains a neuronal-specific activation domain.

Brn-3a, Brn-3b and Brn-3c are closely related POU family transcription factors which are expressed predominantly in neuronal cells. Previously Brn-3a has been shown to activate a number of gene promoters in co-transfections carried out in different cell types, while Brn-3b inhibits the basal activity of these promoters. We show here that Brn-3c activates the same promoters as Brn-3a but only in co-transfections into neuronal cells and not in other cell types.

POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element.

The estrogen receptor (ER) modulates transcription by forming complexes with other proteins and then binding to the estrogen response element (ERE). We have identified a novel interaction of this receptor with the POU transcription factors Brn-3a and Brn-3b which was independent of ligand binding. By pull-down assays and the yeast two-hybrid system, the POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER.