Preferential transcription and nuclear transport of globin gene sequences, as control steps leading to final differentiation of murine erythroleukemic cells.
Murine erythroleukemic (MEL) cells undergo a specific program of differentation in vitro, which is mainly characterized by accumulation of globin mRNA. These cells serve as a model system to study in detail the expression of a specific gene product at the transcriptional and post-transcriptional level. In this report we describe experiments in which the transcription rate of globin and non-globin genes, as well as their cytoplasmic appearance, was measured during the differentiation process. Two independent steps for regulating the abundance of globin mRNA were observed. On the transcriptional level we have observed that, in contrast to the transcription of globin genes, the transcription rate of non-globin genes is dramatically reduced throughout the period of induction. When the rate of cytoplasmic appearance was measured newly synthesized globin RNA molecules were found to be preferentially transported into the cytoplasm. It was shown that the reduction in cytoplasmic appearance of nonglobin genes is not a result of a shut-off in their transcriptional activity. In cells treated with 12-O-tetradecanoylphorbol 13-acetate the transcription rate remains constant while a continuous reduction in the cytoplasmic appearance is observed. These two independent phenomena which affect the non-globin genes, i.e. the suppression of their transcription and reduced cytoplasmic appearance, lead to the reduction in the relative amounts of the stable poly(A)-rich mRNA population and to the accumulation of globin sequences in the cytoplasm of the differentiated erythroid cells. These observations are in agreement with our previous model, which claimed that disappearance of the stable poly(A)-rich mRNA population is an obligatory process leading to the final differentiation of MEL cells.
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002999:Clone Cells; D004247:DNA / Q000378:metabolism; D005796:Genes; D005914:Globins / Q000235:genetics*; D007700:Kinetics; D007942:Leukemia, Experimental / Q000503:physiopathology*; D051379:Mice; D009693:Nucleic Acid Hybridization; D014158:Transcription, Genetic
D005914:Globins; D004247:DNA