title: The Oct-1 POU-specific domain can stimulate small nuclear RNA gene transcription by stabilizing the basal transcription complex SNAPc.
abstract: The RNA polymerase II and III human small nuclear RNA promoters have a common basal element, the proximal sequence element, which binds the TATA box-binding protein-containing complex SNAPc. They also contain an enhancer characterized by a highly conserved octamer sequence, which constitutes a binding site for the broadly expressed POU domain transcription factor Oct-1. The POU domain is a bipartite DNA-binding domain consisting of a POU-homeo (POUH) domain and a POU-specific (POUs) domain joined by a flexible linker. Here, we show that the Oct-1 POU domain but not the related Pit-1 POU domain can facilitate the binding of SNAPc to the proximal sequence element, and activate transcription. The effect is probably mediated by protein-protein contacts, and 1 of 30 amino acid differences between the Oct-1 and Pit-1 POUs domains is the key determinant for the differential interaction with SNAPc and the ability to activate transcription. These results show that a function that is the hallmark of activation domains, namely, recruitment of a basal transcription complex resulting in activation of transcription, can be performed by a DNA-binding domain. In this case, subtle changes between activator DNA-binding domains, as subtle as a single amino acid difference, can profoundly affect interaction with the basal transcription machinery.
authors.affiliation: Howard Hughes Medical Institute, State University of New York at Stony Brook, New York 11794, USA.
authors.forename: V
authors.initials: V
authors.lastname: Mittal
authors.forename: M A
authors.initials: MA
authors.lastname: Cleary
authors.forename: W
authors.initials: W
authors.lastname: Herr
authors.forename: N
authors.initials: N
authors.lastname: Hernandez
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005801:Genes, Homeobox; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016385:TATA Box; D035181:TATA-Box Binding Protein; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D015345:Oligonucleotide Probes; C494187:POU1F1 protein, human; C494165:POU2F1 protein, human; C058435:POU2F2 protein, human; D012342:RNA, Small Nuclear; D011993:Recombinant Fusion Proteins; D035181:TATA-Box Binding Protein; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D005982:Glutathione Transferase; D012319:RNA Polymerase II; D012318:RNA Polymerase I