Genetics, Vol 142, 927-934, Copyright © 1996

INVESTIGATIONS

Multiple Pathways for Steel Regulation Suggested by Genomic and Sequence Analysis of the Murine Steel Gene

M. A. Bedell, N. G. Copeland and N. A. Jenkins
Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201

The Steel (Sl) locus encodes mast cell growth factor (Mgf) that is required for the development of germ cells, hematopoietic cells and melanocytes. Although the expression patterns of the Mgf gene are well characterized, little is known of the factors which regulate its expression. Here, we describe the cloning and sequence of the full-length transcription unit and the 5' flanking region of the murine Mgf gene. The full-length Mgf mRNA consists of a short 5' untranslated region (UTR), a 0.8-kb ORF and a long 3' UTR. A single transcription initiation site is used in a number of mouse tissues and is located just downstream of binding sites for several known transcription factors. In the 5' UTR, two ATGs were found upstream of the initiator methionine and are conserved among different species, suggesting that Mgf may be translationally regulated. At least two Mgf mRNAs are produced by alternative use of polyadenylation sites, but numerous other potential polyadenylation sites were found in the 3' UTR. In addition, the 3' UTR contains numerous sequence motifs that may regulate Mgf mRNA stability. These studies suggest multiple ways in which expression of Mgf may be regulated.

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