Dexamethasone stimulates rRNA gene transcription in rat myoblasts.
The glucocorticoid analogue, dexamethasone, stimulated RNA synthesis more than two-fold in rat L6 myoblasts, without affecting the rate of cell proliferation. Treatment of myoblasts for 24 h with 10(-7) M dexamethasone resulted in a 30% increase in the cellular RNA level. More than a two-fold stimulation of pre-rRNA gene transcription by dexamethasone, as measured in isolated nuclei and by cell-free transcription, was accompanied by a corresponding increase in pre-rRNA levels. Co-incubation of myoblasts with cycloheximide and dexamethasone did not affect the enhanced pre-rRNA gene transcription demonstrating that de novo protein synthesis was unnecessary to manifest the dexamethasone effect on rDNA transcription. Support for this conclusion is provided by the finding that the levels of UBF1 and UBF2, rDNA upstream binding transcription factors, remain unchanged. The glucocorticoid antagonist RU38486 [11 beta-(4-dimethylaminophenyl)17 beta-hydroxy-17 alpha-(prop-1-ynyl)estra- 4,9-dien-3-one] inhibited the dexamethasone-stimulated rRNA gene transcription suggesting that the glucocorticoid receptor is involved in the response mechanism.
Glibetic
M
M
Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada.
Larson
D E
DE
Rothblum
L I
LI
Sells
B H
BH
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D009132:Muscles / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D009447:Neuroblastoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D035463:Pol1 Transcription Initiation Complex Proteins; D012318:RNA Polymerase I / Q000032:analysis / Q000378:metabolism; D012335:RNA, Ribosomal / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; C063844:transcription factor UBF; D015735:Mifepristone; D003907:Dexamethasone; D004247:DNA; D003513:Cycloheximide; D012318:RNA Polymerase I