Characterization of human cytoglobin gene promoter region.
Cytoglobin (CYGB) is a member of the vertebrate globin family together with hemoglobin, myoglobin and neuroglobin. Although the physiological function of CYGB is still unclear, spectroscopic studies show that CYGB contains a hexacoordinated heme pocket similar to other pentacoordinated globin proteins. CYGB shares a common phylogenetic ancestry with vertebrate myoglobin from which it diverged by duplication before the appearance of jawed vertebrates. The objective of this study is to identify the regulatory and promoter region of the human cytoglobin gene. 5' unidirectional deletion constructs demonstrated that the proximal promoter elements of human CYGB gene are located between -1113 to -10 relative to the translation start site. Site-directed mutagenesis showed that mutation of a c-Ets-1 motif at -1008 and Sp1 motifs at -400, -230 and -210 remarkably decreased the promoter activity. Gel shift assays confirmed the binding of DNA-nuclear proteins to these motifs. All these results indicate that CYGB gene expression can be up-regulated by c-Ets-1 and Sp1 motifs.
Guo
Xiumei
X
Department of Zoology, The University of Hong Kong, Hong Kong SAR.
Philipsen
Sjaak
S
Tan-Un
Kian-Cheng
KC
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D000078842:Cytoglobin; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation
C000627265:CYGB protein, human; D000078842:Cytoglobin; D050784:Proto-Oncogene Protein c-ets-1; D016329:Sp1 Transcription Factor; D005914:Globins