CIS-ACTING DNA ELEMENTS OF MOUSE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENE RESPONSIVE TO FC-EPSILON RECEPTOR CROSS-LINKING STIMULATION IN THE MOUSE MAST-CELL LINE MC 9/
R. Nishikomori et al., CIS-ACTING DNA ELEMENTS OF MOUSE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENE RESPONSIVE TO FC-EPSILON RECEPTOR CROSS-LINKING STIMULATION IN THE MOUSE MAST-CELL LINE MC 9/, The Journal of immunology, 154(2), 1995, pp. 694-702
Mouse mast cells produce many kinds of cytokines in response to cross-
linking of high affinity Fc epsilon receptor (Fc epsilon RI). Among th
ese cytokines, granulocyte-macrophage CSF (GM-CSF) gene induction in m
ouse mast cells has been reported to be regulated at both the transcri
ptional level and the post-transcriptional level. We analyzed the mech
anism of the transcriptional regulation of GM-CSF gene induction throu
gh Fc epsilon RI cross-linking stimulation in the mouse mast cell line
MC/9. In MC/9, the GM-CSF gene was activated transcriptionally by Fc
epsilon RI cross-linking stimulation. The 5' deletion analysis of GM-C
SF gene promoter indicated that the 5' boundary of the responsive prom
oter region lay between positions -113 and -95. When the deletion was
extended to positions -72 or -60, the stimulatory effect was significa
ntly diminished. We then examined 3' deletion of pmGMCAT-113 from posi
tion -60. This analysis indicated that the 3' boundary lay between pos
itions -84 and -72. No subfragments of the region spanning positions -
113 to -72 could cover the full induction level. A site-directed mutag
enesis experiment revealed that the sequence spanning positions -108 t
o -72 was needed for full activation. These data indicate that GM-CSF
gene in mast cells is activated mainly through the sequence spanning p
ositions -108 to -72.