Role of dexamethasone in globin gene expression in differentiating Friend cells

• Published in: The Journal of biological chemistry Vol. 256; no. 13; pp. 6736 - 6741
• Main Authors: R C Mierendorf, Jr, G C Mueller
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 10-07-1981
• Subjects: Animals; Cell Differentiation - drug effects; Cell Line; Clone Cells; Dexamethasone - pharmacology; Genes - drug effects; Globins - genetics; Kinetics; Leukemia, Experimental - metabolism; Mice; Protein Biosynthesis - drug effects; RNA, Messenger - genetics; Transcription, Genetic - drug effects
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)69053-8

The expression of the globin genes which accompanies the chemically induced differentiation of Friend erythroleukemia cells
is subject to inhibition by glucocorticoid hormones. The present study inquires into the possible mechanisms for this suppression.
It is shown that the synthetic glucocorticoid, dexamethasone, can both prevent the initial appearance of beta-globin mRNA
during the induction of differentiation and inhibit the ongoing production of this RNA in induced cells. Isolated nuclei from
dexamethasone-treated cells also exhibited a depressed ability to synthesize beta-globin mRNA. These effects were achieved
without altering the turnover rate of the mature messenger RNA. Electrophoretic analysis of pulse-labeled transcripts before
and after a chase interval indicated that large Mr beta-globin precursor molecules were processed normally to mature nuclear
beta-globin mRNA in cells treated with dexamethasone. S1 nuclease protection experiments showed further that dexamethasone
treatment of induced cells uniquely depressed the amount of precursor-specific beta-globin sequences contained in unlabeled
nuclear RNA preparations. The data support the view that dexamethasone regulates globin gene expression at or very close to
the transcriptional level.