Gestational age-related patterns of AMOT methylation are revealed in preterm infant endothelial progenitors.

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Version: Final published version
Serval ID
serval:BIB_F79E5DFB6FE8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gestational age-related patterns of AMOT methylation are revealed in preterm infant endothelial progenitors.
Journal
PloS one
Author(s)
Vinci G., Buffat C., Simoncini S., Boubred F., Ligi I., Dumont F., Le Bonniec B., Fournier T., Vaiman D., Dignat-George F., Simeoni U.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
12
Number
10
Pages
e0186321
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Preterm birth is associated with altered angiogenesis and with increased risk of cardiovascular dysfunction and hypertension at adulthood. We previously demonstrated that in preterm newborns circulating cord blood endothelial progenitor cells (ECFC), responsible for angio/vasculogenesis, are reduced in number and display altered angiogenic properties. Altered angiogenic function was associated with a decreased expression of pro-angiogenic genes, among which the AMOT gene which is a strong positive regulator of angiogenesis. Such dysregulation may be related to epigenetic factors. In this study we analyse the methylation profiling of the AMOT gene during development, through a comparative analysis of the cord blood ECFC of preterm newborns and their term counterpart.
We used both cloning-sequencing and pyrosequencing experiments to perform a comparative analysis of the DNA methylation profile of the promoter CpG island of AMOT gene in the cord blood ECFC of 16 preterm newborns (28-35 weeks gestational age-GA) and 15 term newborns (>37 weeks GA).
Twenty nine clones (obtained from 2 term newborns) and forty clones (obtained from 3 preterm newborns) were sequenced. The AMOT gene methylation rate was significantly higher in preterm compared to term newborns (4.5% versus 2.5% respectively: χ2 = 3.84; P = 1.8 10-02). Bisulfite pyrosequencing identified four CpG dinucleotides with significantly higher methylation levels in preterm newborns. This CpG-targeted methylation significantly decreased with increasing gestational age.
These findings highlight importance of pro-angiogenic AMOT gene methylation in ECFC, suggesting that epigenetic mechanisms may control the regulation of angiogenesis during development. Therefore they pave the way to specific short term and long term complications of preterm birth by altered angiogenesis.

Keywords
Adult, CpG Islands, DNA Methylation, Endothelial Progenitor Cells/metabolism, Epigenesis, Genetic, Female, Fetal Blood/metabolism, Humans, Infant, Premature/growth & development, Infant, Premature/metabolism, Infant, Small for Gestational Age/growth & development, Infant, Small for Gestational Age/metabolism, Intercellular Signaling Peptides and Proteins/genetics, Intercellular Signaling Peptides and Proteins/metabolism, Male, Maternal Age, Membrane Proteins/genetics, Membrane Proteins/metabolism, Promoter Regions, Genetic, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA
Pubmed
Web of science
Open Access
Yes
Create date
02/11/2017 14:14
Last modification date
20/08/2019 16:23
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