Transcription of the human cell cycle regulated BUB1B gene requires hStaf/ZNF143.
BubR1 is a key protein mediating spindle checkpoint activation. Loss of this checkpoint control results in chromosomal instability and aneuploidy. The transcriptional regulation of the cell cycle regulated human BUB1B gene, which encodes BubR1, was investigated in this report. A minimal BUB1B gene promoter containing 464 bp upstream from the translation initiation codon was sufficient for cell cycle regulated promoter activity. A pivotal role for transcription factor hStaf/ZNF143 in the expression of the BUB1B gene was demonstrated through gel retardation assays, transient expression of mutant BUB1B promoter-reporter gene constructs and chromatin immunoprecipitation assay. Two phylogenetically conserved hStaf/ZNF143-binding sites (SBS) were identified which are indispensable for BUB1B promoter activity. In addition, we found that the domain covering the transcription start sites contains conserved boxes homologous to initiator (Inr), cell cycle dependent (CDE) and cell cycle genes homology regions (CHR) elements. Mutations within the CDE and CHR elements led to diminished cell cycle regulation of BUB1B transcription. These results demonstrate that BUB1B gene transcription is positively regulated by hStaf/ZNF143, a ubiquitously expressed factor, and that the CDE-CHR tandem element was essential for G2/M-specific transcription of the BUB1B gene.
Myslinski
Evelyne
E
Architecture et Réactivité de l'ARN, Université Louis Pasteur de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg, France.
Gérard
Marie-Aline
MA
Krol
Alain
A
Carbon
Philippe
P
D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D002522:Chlorocebus aethiops; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila / Q000166:cytology / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D015534:Trans-Activators; C114253:ZNF143 protein, human; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases