MYBBP1a is a novel repressor of NF-kappaB.

NF-kappaB is an inducible transcription factor activated in many different cell types by inflammatory and stress signals. The transcription of a wide variety of NF-kappaB genes is regulated by the coordinated action of transcription co-activators and co-repressors. Previously we identified Myb binding protein 1a (MYBBP1a) as an interaction partner of the transcription activation domain of RelA/p65. MYBBP1a has been shown by others to regulate various transcription factors, through largely unknown mechanisms. Here we present evidence that MYBBP1a is a novel co-repressor of NF-kappaB. MYBBP1a interacted directly with RelA/p65 and expression of MYBBP1a in cells repressed NF-kappaB dependent reporter expression but did affect neither RelA/p65 nuclear translocation nor its DNA binding activity. In vitro, MYBBP1a inhibited transcription from chromatinized templates at a step before pre-initiation complex formation. MYBBP1a was found to compete with the histone acetyl transferase co-activator, p300, for interaction with the transcription activation domain of RelA/p65. Expression levels of MYBBP1a are dependent on the cell type, and are particularly high in Jurkat T cells. These results indicate that MYBBP1a is a novel NF-kappaB co-repressor of transcription that competes with p300 and may function to regulate cell type specific genes.