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Int. J. Mol. Sci. 2018, 19(4), 1069; https://doi.org/10.3390/ijms19041069

Cell-Specific PEAR1 Methylation Studies Reveal a Locus that Coordinates Expression of Multiple Genes

1
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, 3000 Leuven, Belgium
2
Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Via dell’Elettronica, 86077 Pozzilli (IS), Italy
*
Author to whom correspondence should be addressed.
Received: 15 February 2018 / Revised: 19 March 2018 / Accepted: 28 March 2018 / Published: 3 April 2018
(This article belongs to the Special Issue DNA Methylation)
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Abstract

Chromosomal interactions connect distant enhancers and promoters on the same chromosome, activating or repressing gene expression. PEAR1 encodes the Platelet-Endothelial Aggregation Receptor 1, a contact receptor involved in platelet function and megakaryocyte and endothelial cell proliferation. PEAR1 expression during megakaryocyte differentiation is controlled by DNA methylation at its first CpG island. We identified a PEAR1 cell-specific methylation sensitive region in endothelial cells and megakaryocytes that showed strong chromosomal interactions with ISGL20L2, RRNAD1, MRLP24, HDGF and PRCC, using available promoter capture Hi-C datasets. These genes are involved in ribosome processing, protein synthesis, cell cycle and cell proliferation. We next studied the methylation and expression profile of these five genes in Human Umbilical Vein Endothelial Cells (HUVECs) and megakaryocyte precursors. While cell-specific PEAR1 methylation corresponded to variability in expression for four out of five genes, no methylation change was observed in their promoter regions across cell types. Our data suggest that PEAR1 cell-type specific methylation changes may control long distance interactions with other genes. Further studies are needed to show whether such interaction data might be relevant for the genome-wide association data that showed a role for non-coding PEAR1 variants in the same region and platelet function, platelet count and cardiovascular risk. View Full-Text
Keywords: PEAR1; DNA methylation; chromosome interactions PEAR1; DNA methylation; chromosome interactions
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Izzi, B.; Noro, F.; Cludts, K.; Freson, K.; Hoylaerts, M.F. Cell-Specific PEAR1 Methylation Studies Reveal a Locus that Coordinates Expression of Multiple Genes. Int. J. Mol. Sci. 2018, 19, 1069.

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