Identification of the control regions for mouse c-kit gene transcription induced by retinoic acid.
The c-kit gene encodes a receptor tyrosine kinase that reveals the pleiotropic effects both in the developing embryo and in the adult animal. In this study, we characterized transcriptional control of the c-kit gene. F9 teratocarcinoma cells differentiated and expressed the c-kit gene upon exposure to retinoic acid (RA). We isolated c-kit genomic DNA from approximately 20 kb upstream to approximately 10 kb downstream of the transcribed region. We identified two control regions for c-kit gene transcription by fusing genomic sequences to bacterial chloramphenicol acetyl transferase reporter genes and introducing the resultant constructs into differentiated F9 cells. The fragments, Sac I-Apa I in the 9th intron and Xho I-Kpn I in the 13th intron induced reporter gene activities. Nucleotide sequencing of the regions showed in that there were no consensus sequences of the RA receptor or cyclic AMP-responsive elements. Cyclic AMP augmented the expression of the c-kit gene induced by RA; when combined with RA, it was less effective on the reporter gene activity. In contrast to other reports, continuous exposure to the reagents was not required for c-kit expression. These findings suggested that transcription of the c-kit gene is regulated by complex controls and that there are different control regions responsive to RA and cyclic AMP.
Hayashi
S
S
Department of Immunology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Japan.
Kunisada
T
T
Ogawa
M
M
Nishikawa
S
S
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D014212:Tretinoin; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit