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Title: | Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages |
Author: | Rangel Salazar, Rubén Wickström-Lindholm, Marie Aguilar Salinas, Carlos A. Alvarado-Caudillo, Yolanda Døssing, Kristina B. V. Esteller, Manel Labourier, Emmanuel Lund, Gertrud Nielsen, Finn C. Rodríguez-Ríos, Dalia Solís Martínez, Martha O. Wrobel, Katarzyna Wrobel, Kazimierz Zaina, Silvio |
Keywords: | Regulació genètica Lipoproteïnes Genetic regulation Lipoproteins |
Issue Date: | 25-Nov-2011 |
Publisher: | BioMed Central |
Abstract: | Background: We previously showed that a VLDL-and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i. e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these epigenetic responses; 2) test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Results: Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1) surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2) independent of the Dicer/microRNA pathway. Conclusions: Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals. |
Note: | Reproducció del document publicat a: https://doi.org/10.1186/1471-2164-12-582 |
It is part of: | BMC Genomics, 2011, vol. 12, num. 582 |
URI: | http://hdl.handle.net/2445/126608 |
Related resource: | https://doi.org/10.1186/1471-2164-12-582 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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