Cell-Specific PEAR1 Methylation Studies Reveal a Locus that Coordinates Expression of Multiple Genes
| Autor: | Marc Hoylaerts, Benedetta Izzi, Fabrizia Noro, Kathleen Freson, Katrien Cludts |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell type Megakaryocyte differentiation Cell Cycle Proteins Receptors Cell Surface Biology Article Catalysis Inorganic Chemistry lcsh:Chemistry 03 medical and health sciences 0302 clinical medicine Gene expression Human Umbilical Vein Endothelial Cells PEAR1 Humans Physical and Theoretical Chemistry Promoter Regions Genetic Molecular Biology Gene lcsh:QH301-705.5 Spectroscopy DNA methylation Organic Chemistry chromosome interactions Promoter General Medicine Methylation Neoplasm Proteins Computer Science Applications Cell biology Exodeoxyribonucleases 030104 developmental biology CpG site lcsh:Biology (General) lcsh:QD1-999 030220 oncology & carcinogenesis CpG Islands Heparin-binding EGF-like Growth Factor |
| Zdroj: | International Journal of Molecular Sciences, Vol 19, Iss 4, p 1069 (2018) International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 19; Issue 4; Pages: 1069 |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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