Characterization of the Gene Encoding Mouse Retinoblastoma Binding Protein-7, a Component of Chromatin-Remodeling Complexes

Abstract

RBBP7 is a highly conserved WD-repeat protein that interacts with histone deacetylases and is a component of several co-repressor complexes. The mouse gene Rbbp7 spans ∼20 kb, consists of at least 12 exons, and contains a C/T polymorphism in the 3′ splice acceptor region of intron 3. We found that Rbbp7 contains a TATA-less promoter with multiple transcription initiation sites. In transient transfection assays, we identified potential positive regulatory elements upstream of the proximal promoter at −668 to −1710. RBBP7 protein is detectable from at least day 9.5 of embryogenesis and is strongly expressed in the developing kidney and brain. Consistent with its association with co-repressor complexes, we demonstrate that RBBP7 represses the c-FOS transactivation domain in response to mitogen stimulation. We have also excluded human RBBP7 as a candidate gene in six patients that exhibit X-linked mental retardation, a heterogeneous developmental disorder that has been linked in some cases to mutations in genes involved in chromatin remodeling.