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PMID: 2046667 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Negative regulation of globin gene expression during megakaryocytic differentiation of a human erythroleukemic cell line.

Molecular and cellular biology ·Vol. 11 ·No. 7 ·1991-07-00 ·Pages 3528-36

Lumelsky NL, Forget BG

Abstract

The human erythroleukemic cell line K562 was used as a model for analysis of the mechanisms responsible for alterations in gene expression during differentiation. K562 cells normally synthesize fetal hemoglobin (gamma-globin), but treatment with tumor-promoting phorbol esters (phorbol myristate acetate and tetradecanoyl phorbol acetate) results in the loss of the erythroid phenotype of the cells and causes a shift toward a megakaryocytic phenotype. This shift involves markedly decreased production of fetal hemoglobin and de novo synthesis of a number of proteins specific for megakaryocytes. The results of this work indicate that negative regulation of fetal hemoglobin during megakaryocytic differentiation of K562 cells occurs at the level of down regulation of gamma-globin mRNA accumulation. This effect consists of at least two components: reduction in the rate of transcription of the gamma-globin gene and decrease in stability of the normally very stable gamma-globin mRNA. We have developed two assay systems that permit investigation of the transcriptional and posttranscriptional effects of phorbol myristate acetate independently from each other. These assay systems make use of a heterologous reporter gene for the transcriptional analysis and a marked gamma-globin gene for the analysis of mRNA stability. The DNA sequences located in the 3' flanking region of the A gamma-globin gene were found to be responsible for the decrease in transcription rate.

MeSH Terms
Cell Differentiation Cell Nucleus/physiology Gene Expression Regulation, Neoplastic/drug effects Globins/genetics Humans Leukemia, Erythroblastic, Acute Megakaryocytes/cytology Phenotype Plasmids RNA, Messenger/genetics,metabolism RNA, Neoplasm/genetics,isolation & purification Restriction Mapping Tetradecanoylphorbol Acetate/pharmacology Transcription, Genetic/drug effects Transfection
Chemicals
RNA, Messenger RNA, Neoplasm Globins Tetradecanoylphorbol Acetate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lumelsky N L
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Forget B G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.11.7.3528-3536.1991
Published
1991-07-00
Pages
3528-36
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361092
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.11.7.3528-3536.1991 PMC Full Text View journal details
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