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Epigenetic control of PRV-1 expression on neutrophils.

Abstract：

OBJECTIVE:Polycythemia rubra vera-1 (PRV-1) is a GPI-linked protein that is expressed on a subgroup of neutrophils. The number of PRV-1-expressing neutrophils increases in pregnancy and sepsis, or after administration of granulocyte colony-stimulating factor. Expression of the PRV-1 gene is also increased in patients with polycythemia vera (PV) and essential thrombocythemia (ET). We investigated whether DNA methylation of the PRV-1 gene has a role in regulation of transcription and expression of the PRV-1 protein. METHODS:We compared the level of methylation of the PRV-1 gene and expression of the PRV-1 mRNA in normal neutrophils expressing PRV-1 to those that are PRV-1-negative. We also studied PRV-1 methylation and mRNA expression in patients with Philadelphia chromosome-negative myeloproliferative disorders and in an in vitro model of DNA demethylation. RESULTS:We found that methylation of CpG dinucleotides close to initiation codon of the PRV-1 gene was inversely related to expression of PRV-1 in normal neutrophils. Furthermore, overexpression of the PRV-1 gene in PV and ET is associated with a decrease in methylation of this gene. Among patients with PV and ET, methylation of the PRV-1 gene is also inversely correlated with the presence of the JAK2(V617F) somatic mutation. In an in vitro model, exposure of KG1 and KG1a cells to a DNA demethylating agent caused a decrease in methylation of the PRV-1 gene and increased its mRNA level. CONCLUSION:DNA methylation regulates PRV-1 expression under physiologic and pathologic conditions.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Jelinek J,Li J,Mnjoyan Z,Issa JP,Prchal JT,Afshar-Kharghan V

doi

10.1016/j.exphem.2007.09.008

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

1677-83

issue

11

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(07)00579-6

journal_volume

35

pub_type

杂志文章

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