TY - JOUR
T1 - Epigenetic control of PRV-1 expression on neutrophils
AU - Jelinek, Jaroslav
AU - Li, Jun
AU - Mnjoyan, Zakar
AU - Issa, Jean Pierre J.
AU - Prchal, Josef T.
AU - Afshar-Kharghan, Vahid
N1 - Funding Information:
Supported by a grant from the Leukemia and Lymphoma Society and Myeloproliferative Foundation (V.A-K), the Department of Veteran Affairs Merit review grant (V.A-K), and the Department of Defense grant W81XWH-05-1-0535 (J.J. and J.P.J.I.).
PY - 2007/11
Y1 - 2007/11
N2 - 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 JAK2V617F 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.
AB - 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 JAK2V617F 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.
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U2 - 10.1016/j.exphem.2007.09.008
DO - 10.1016/j.exphem.2007.09.008
M3 - Article
C2 - 17976520
AN - SCOPUS:35448933152
SN - 0301-472X
VL - 35
SP - 1677.e1-1677.e8
JO - Experimental Hematology
JF - Experimental Hematology
IS - 11
ER -