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Genomics. 1994 Mar 1;20(1):5-12.

Structure and transcription of the human c-mpl gene (MPL).

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  • 1Institut National de la Santé et de la Recherche Médicale, U. 91, Hôpital Henri Mondor, Creteil, France.

Abstract

The human c-mpl proto-oncogene encodes a member of the cytokine receptor superfamily, expressed mainly in CD 34-positive hematopoietic progenitors and in the megakaryocytic lineage. To investigate the elements required for this tissue-specific expression, we cloned the human c-mpl 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 different proteins, are generated. The major species contains all 12 exons; mRNAs encoding a protein with a smaller cytoplasmic domain are produced by termination of the transcript within intron 10, and mRNAs encoding 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 proteins of the Ets and GATA families. Finally, we show that a 700-bp fragment of the human c-mpl promoter is active in the HEL and K562 cell lines, which express erythroid and megakaryocytic markers, but is inactive in the nonhematopoietic HeLa cell line and the Jurkat T lymphoid cell line.

PMID:
8020956
[PubMed - indexed for MEDLINE]
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