Regulation of human globin gene expression in mouse erythroleukemia x human fibroblast hybrid cells.
A somatic cell hybrid, XX-8, was obtained from a fusion of tetraploid mouse erythroleukemia cells with human Lesch-Nyhan skin fibroblasts. This hybrid cell was previously shown (1) to produce human beta- but no human gamma-globin mRNA sequences after induction with dimethylsulfoxide. In this study we show that: (a) human beta- and gamma-globin genes are present in XX-8 cells in approximately equal numbers; (b) no human gamma-globin mRNA sequences can be detected in either the cytoplasmic or nuclear RNA fractions even with several different inducers; (c) after induction the human beta-globin gene is converted from a DNase I insensitive or closed structure to a DNase I open configuration, while the human gamma-globin gene remains closed; and (d) no human beta-globin polypeptide can be detected in the intact induced cells, indicating that fibroblast globin genes, even when induced to make mRNA in an erythroid environment, do not synthesize an RNA that is translated efficiently.
Vembu
D
D
Laboratory of Molecular Hematology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20205, USA.
Young
N S
NS
Willing
M
M
Church
E
E
Sanders-Haigh
L
L
Anderson
W F
WF
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D018076:DNA, Complementary; D003851:Deoxyribonucleases; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006427:Hemin / Q000494:pharmacology; D006441:Hemoglobin A / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects / Q000502:physiology*; D007926:Lesch-Nyhan Syndrome; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000166:cytology; D004113:Succimer / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology; D005719:gamma-Globulins / Q000235:genetics*
D000081:Acetamides; D000970:Antineoplastic Agents; D002614:Chelating Agents; D018076:DNA, Complementary; D012333:RNA, Messenger; D005719:gamma-Globulins; D006427:Hemin; D006441:Hemoglobin A; D004113:Succimer; D003851:Deoxyribonucleases; C014026:hexamethylene bisacetamide