Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages

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Bibtex

@article{fc81de0c6ec342909a7334f436957f7e,
title = "Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages",
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.",
author = "Ruben Rangel-Salazar and Marie Lindholm and Aguilar-Salinas, {Carlos A.} and Yolanda Alvarado-Caudillo and Dossing, {Kristina Bv} and Manel Esteller and Emmanuel Labourier and Gertrud Lund and Nielsen, {Finn C.} and Dalia Rodriguez-Rios and Solis-Martinez, {Martha O.} and Katarzyna Wrobel and Kazimierz Wrobel and Silvio Zaina",
year = "2011",
doi = "10.1186/1471-2164-12-582",
language = "English",
volume = "12",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central (BMC)",

}