Regulation of globin gene expression in human K562 cells by recombinant
activin A
NL Frigon , L Shao, AL Young, L Maderazo and J Yu
Department of Molecular and Experimental Medicine, Scripps Research
Institute, La Jolla, CA 92037.
Recent studies indicate that a purified protein, activin A, belongs to the
transforming growth factor beta (TGF-beta) superfamily. Similar to
TGF-beta, activin A can have different biologic activities, depending on
the target tissues. We used recombinant activin A to demonstrate a possible
regulatory role of this protein in modulating human erythroid
differentiation in the human erythroid cell line, K562. Using genomic
probes containing the second exon of alpha, beta, gamma, and epsilon
globins, relative abundance of various types of globin transcripts in
untreated and activin-treated K562 cells was examined with S1 nuclease
analysis. Despite considerable homology amongst various globin sequences,
these globin probes were highly specific for their unique mRNA species in
the analyses. It was shown that the abundance of specific globin probe
fragments for gamma and epsilon globins (209 nucleotides) as well as alpha
(180 nucleotides), which were protected from S1 digestion, increased many
fold in K562 cells treated with activin A. In contrast, there were no
specific transcripts of beta globin detected in either the control or
activin-treated cells. The increases in the level of fetal and embryonic
beta-like and alpha globin transcripts also confirmed earlier studies of
Northern and slot- blot analyses using globin cDNA as probes. In addition,
nuclear run-off transcription assay using isolated nuclei indicated that
most of the increase in the globin transcripts after activin treatment
could be attributed to the stimulation of transcription rate for globin
genes. Transient transfection assays also provide evidence that activin A
significantly stimulated transcriptional activity of an epsilon globin
promoter in K562, but not in the nonerythroid Chinese hamster ovary cells.
Therefore, it was concluded that activin A exerts its effects on globin
gene expression at the level of transcription in erythroid cells.
Volume 79,
Issue 3,
pp. 765-772,
02/01/1992
Copyright © 1992 by The American Society of Hematology
