Document Detail

Regulation of gene expression of myeloperoxidase during myeloid differentiation.
MedLine Citation:
PMID:  2842344     Owner:  NLM     Status:  MEDLINE    
Myeloperoxidase (MPO) is a major heme enzyme involved in inflammatory responses of polymorphonuclear leukocytes. Using cDNA and intron specific probes for MPO we studied the regulation of MPO expression during myeloid differentiation of the promyelocytic HL-60 leukemia cell line. Mature MPO mRNA species of 3.3, 2.8 and 1.6 kb and heterogeneous nuclear (hn) RNA of greater than 8 and approximately 4 kb were observed in wildtype HL-60 cells. Induction of differentiation of the cells towards either granulocytes or macrophages resulted in a profound decrease (greater than 95%) in the concentration of MPO mRNA levels, showing that gene expression of MPO mRNA is closely linked to the stage of development of myeloid cells. Studies using normal and leukemic hematopoietic cells confirmed these findings and showed that myeloblasts and promyelocytes contain MPO mRNA. Rate of transcription of MPO was measured by a nuclear run-on assay in wild-type and day 3- and day -4 differentiated HL-60 cells and was nearly the same in all three. In contrast, rate of transcription of c-myc in the same nuclei became almost undetectable with induction of differentiation. Overall transcription decreased by 60% and 80% on day 3 and 4 of differentiation, respectively, compared to wild-type cells. Stability of mature MPO mRNA was also measured and found to be the same in wild-type and differentiated HL-60. Half-life of MPO hnRNA was less than or equal to 30 min in wild-type HL-60; nevertheless, this hnRNA was easily detectable 3 days after induction of differentiation of these cells. Taken together, the results show that decreased expression of MPO mRNA with differentiation occurs in part post-transcriptionally, possibly due to a failure in RNA processing. In addition, as overall transcription decreases during differentiation, MPO transcription is concomitantly reduced. This indicates that transcriptional and post-transcriptional mechanisms cooperate in the control of MPO gene expression.
A Tobler; C W Miller; K R Johnson; M E Selsted; G Rovera; H P Koeffler
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  136     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1988 Aug 
Date Detail:
Created Date:  1988-09-29     Completed Date:  1988-09-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  215-25     Citation Subset:  IM    
Department of Medicine, UCLA Medical Center 90024.
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MeSH Terms
Cell Differentiation
Gene Expression Regulation*
Leukemia, Myeloid, Acute / enzymology*,  genetics
Macrophages / cytology
Peroxidase / genetics*
RNA, Heterogeneous Nuclear / analysis
RNA, Messenger / metabolism
Grant Support
Reg. No./Substance:
0/RNA, Heterogeneous Nuclear; 0/RNA, Messenger; EC

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