Strong induction of the Tis11B gene in myogenic differentiation.
TIS11B is a zinc-finger protein of the tristetraprolin (TTP) family. Using cDNA microarray analysis, we could identify the Tis11B gene based on its differential expression in myogenesis. Here, we demonstrate that expression of the Tis11B gene is strongly induced during differentiation of the murine myoblast cell line C2C12. By contrast, expression of Ttp itself was not induced in myogenesis. Pretreatment of the cells with the translation inhibitor cycloheximide demonstrated that Tis11B was a primary response gene in this process. In addition, pretreatment with the transcription inhibitor actinomycin D demonstrated that gene expression was regulated at the transcriptional level. Since specific inhibitors of p38 MAP kinase completely blocked Tis11B induction, we conclude that expression of the Tis11B gene is regulated at least in part by this signaling pathway which plays a central role in myogenesis. Induction of Tis11B expression was also observed in primary myoblasts isolated from two different mouse strains, indicating physiological relevance of our results. In addition, TIS11B might also be an important player during myogenic differentiation and regeneration in vivo, as we detected a marked decrease in expression in several muscle tissues of the dystrophic mdx mouse, a model for continuous muscle degeneration and regeneration. These data suggest that TIS11B is an important regulator of myogenesis.
Busse
Melanie
M
Institute of Physiology, Charité - University Medicine Berlin, Arnimallee 22, D-14195 Berlin, Germany.
Schwarzburger
Max
M
Berger
Felicitas
F
Hacker
Christine
C
Munz
Barbara
B
D000818:Animals; D051817:Butyrate Response Factor 1; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology*; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D051817:Butyrate Response Factor 1; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D016601:RNA-Binding Proteins; C488431:Zfp36l1 protein, mouse; D003609:Dactinomycin; D003513:Cycloheximide; D048051:p38 Mitogen-Activated Protein Kinases