STRUCTURE AND TRANSCRIPTION OF THE HUMAN C-MPL GENE (MPL)

The human c-mpl proto-oncogene encodes a member of the cytokine recept or superfamily, expressed mainly in CD 34-positive hematopoietic proge nitors and in the megakaryocytic lineage. To investigate the elements required for this tissue-specific expression, we cloned the human c-np l gene (MPL) as well as the 5' end of the mouse gene. The human c-mpl gene contains 12 exons distributed over 17 kb of DNA. Each of the two ''cytokine receptor domains'' of Mpl is encoded by a set of four exons , the transmembrane domain by a single exon and the cytoplasmic domain by two exons. We also describe how three types of mRNA, encoding diff erent proteins, are generated. The major species contains all 12 exons ; mRNAs encoding a protein with a smaller cytoplasmic domain are produ ced by termination of the transcript within intron 10, and mRNAs encod ing a putative soluble form of the c-Mpl protein lack exons 9 and 10. The promoter regions of the human and mouse genes were characterized. These promoters are GC-rich and contain putative binding sites for pro teins of the Ets and GATA families. Finally, we show that a 700-bp fra gment of the human c-mpl promoter is active in the HEL and K562 cell l ines, which express erythroid and megakaryocytic markers, but is inact ive in the nonhematopoietic HeLa cell line and the Jurkat T lymphoid c ell line. (C) 1994 Academic Press, Inc.