title: An initiator and its flanking elements function as a core promoter driving transcription of the Hepatopoietin gene.
abstract: Hepatopoietin (HPO)/ALR (augmenter of liver regeneration), as a versatile hepatotrophic growth factor and a cellular thiol oxidase, is involved in a wide variety of basic processes of various tissues, especially in liver and testis. Here, we studied the regulation of HPO gene expression. By sequential deletion of the HPO 5'-flanking region, the minimal promoter of the HPO gene was shown to span positions -22 to +42 relative to the transcriptional start point. Further transfection assay and mutation analysis showed that the core promoter contains a functional initiator. Interestingly, three tandem repeats of a CTGGAGGC element, surrounding the transcription start site and bound by specific nuclear factors, were found to be pivotal for the promoter activity. This initiator flanking element functions in an initiator-dependent fashion and is present in many initiator-containing genes. Taken together, our findings revealed that the initiator-like element and its flanking repeat sequence comprise a core promoter and drive the transcriptional initiation of the HPO gene in a combinatorial manner. The HPO gene promoter might represent a novel architecture for core promoters.
authors.affiliation: Department of Proteomics and Genomics, Beijing Institute of Radiation Medicine, Chinese Human Genome Center at Beijing, 27 Taiping Road, Beijing 100850, PR China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Zhao
authors.forename: Fei
authors.initials: F
authors.lastname: Tang
authors.forename: Jingwei
authors.initials: J
authors.lastname: Cheng
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Guichun
authors.initials: G
authors.lastname: Xing
authors.forename: Yunping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
authors.forename: Handong
authors.initials: H
authors.lastname: Wei
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
mesh_terms: D001483:Base Sequence; D004247:DNA; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D017228:Hepatocyte Growth Factor; D004247:DNA