Induction of globin mRNA expression by interleukin-3 in a stem cell factor-dependent SV-40 T-antigen-immortalized multipotent hematopoietic cell line.
Erythropoiesis requires the stepwise action on immature progenitors of several growth factors, including stem cell factor (SCF), interleukin 3 (IL-3), and erythropoietin (Epo). Epo is required to sustain proliferation and survival of committed progenitors and might further modulate the level of expression of several erythroid genes, including globin genes. Here we report a new SCF-dependent immortalized mouse progenitor cell line (GATA-1 ts SCF) that can also grow in either Epo or IL-3 as the sole growth factor. When grown in SCF, these cells show an "open" chromatin structure of the beta-globin LCR, but do not significantly express globin. However, Epo or IL-3 induce globin expression and are required for its maintainance. This effect of IL-3 is unexpected as IL-3 was previously reported either to be unable to induce hemoglobinization, or even to antagonize it. This suggests that GATA-1 ts SCF cells may have progressed to a stage in which globin genes are already poised for expression and only require signal(s) that can be elicited by either Epo or IL-3. Through the use of inhibitors, we suggest that p38 may be one of the molecules modulating induction and maintenance of globin expression.
Cairns
Linda
L
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy.
Cirò
Marco
M
Minuzzo
Mario
M
Morlé
François
F
Starck
Joëlle
J
Ottolenghi
Sergio
S
Ronchi
Antonella
A
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D000952:Antigens, Polyomavirus Transforming; D002461:Cell Line, Transformed; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005914:Globins / Q000096:biosynthesis* / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006454:Hemoglobins / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D000943:Antigens, Differentiation; D000952:Antigens, Polyomavirus Transforming; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D007377:Interleukin-3; D012333:RNA, Messenger; D019089:Stem Cell Factor; D004921:Erythropoietin; D005914:Globins; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases