Identification of the control regions for mouse c-kit gene transcription induced by retinoic acid.

Abstract

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.