An initiator and its flanking elements function as a core promoter driving transcription of the Hepatopoietin gene.
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.
Zhao
Yanlin
Y
Department of Proteomics and Genomics, Beijing Institute of Radiation Medicine, Chinese Human Genome Center at Beijing, 27 Taiping Road, Beijing 100850, PR China.
Tang
Fei
F
Cheng
Jingwei
J
Li
Li
L
Xing
Guichun
G
Zhu
Yunping
Y
Zhang
Lingqiang
L
Wei
Handong
H
He
Fuchu
F
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
D017931:DNA Primers; D017228:Hepatocyte Growth Factor; D004247:DNA