Epigenetic control of PRV-1 expression on neutrophils.
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.


CONCLUSIONS
DNA methylation regulates PRV-1 expression under physiologic and pathologic conditions.
Jelinek
Jaroslav
J
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Li
Jun
J
Mnjoyan
Zakar
Z
Issa
Jean-Pierre J
JP
Prchal
Josef T
JT
Afshar-Kharghan
Vahid
V
D002460:Cell Line; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D058851:GPI-Linked Proteins; D006801:Humans; D007519:Isoantigens / Q000235:genetics*; D053614:Janus Kinase 2 / Q000032:analysis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism*; D011087:Polycythemia Vera / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics
C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D007519:Isoantigens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D053614:Janus Kinase 2