Epigenetic modulators, modifiers and mediators in cancer aetiology and progression

Abstract

This year is the tenth anniversary of the publication in this journal of a model suggesting the existence of ‘tumour progenitor genes’. These genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, and thus cause altered differentiation throughout tumour evolution. The past decade of discovery in cancer epigenetics has revealed a number of similarities between cancer genes and stem cell reprogramming genes, widespread mutations in epigenetic regulators, and the part played by chromatin structure in cellular plasticity in both development and cancer. In the light of these discoveries, we suggest here a framework for cancer epigenetics involving three types of genes: ‘epigenetic mediators’, corresponding to the tumour progenitor genes suggested earlier; ‘epigenetic modifiers’ of the mediators, which are frequently mutated in cancer; and ‘epigenetic modulators’ upstream of the modifiers, which are responsive to changes in the cellular environment and often linked to the nuclear architecture. We suggest that this classification is helpful in framing new diagnostic and therapeutic approaches to cancer.

The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells

“…Besides the large blocks of DNA hypomethylation (Hansen et al 2011;Berman et al 2012;Hon et al 2012;Timp et al 2014) and hypermethylation Coolen et al 2010;Forn et al 2013), other alterations as the activation of gene clusters (Bert et al 2013) and the increased somatic mutation rates observed in heterochromatic and late replicating regions (Schuster-Böckler and Lehner 2012;Polak et al 2015) point out that factors regulating high-order chromatin architecture (Dekker et al 2013;Gómez-Díaz and Corces 2014;Feinberg et al 2016) might play a principal role in the remodeling of the cancer genome (Rodriguez et al 2008a;Lizardi et al 2011;Kemp et al 2014;Lay et al 2015;Taberlay et al 2016). The contribution of Alu repeats to the setting and maintenance of chromatin domains and their regulation in normal and cancer cells is still unknown.…”

(Trans‑)Generationale Weitergabe früher Traumatisierung auf das kardiovaskuläre System

“…Durch die Entwicklungen in der epigenetischen Forschung versteht man immer mehr über die biologischen Zusam- (Argentieri et al 2017;Feinberg et al 2016). Auch für die kardiovaskuläre Regulation (Sartori et al 2016), aber ebenso für kardiovaskuläre Risikofaktoren wie das metabolische Syndrom konnten systematische Veränderungen epigenetischer Markierungen nachgewiesen werden (Park et al 2017 (Spitzer et al 2016;Su et al 2015).…”

Epigenetic Modification of Ten Eleven Translocase Enzyme Mediated Hydroxymethylcytosine in Brain Derived Neurotrophic Factor for the Pathogenesis of Type II Diabetes Retinopathy

“…Quantitative Figure 1: Methods of DNA methylation analysis by Lanlan Shena and Robert A. Waterlandb [26] 3 Mechanism Of Dna Demethylation DNA demethylation mechanism is found to be mediated by the ten-eleven translocation (Tet) enzymesTet1, Tet2, and Tet3 [14] . Tet In the first, iterative oxidation by Tet enzymes continues to oxidize 5hmC first to 5-formyl-cytosine and then to 5-carboxy-cytosine In the second,5hmC is deaminated by AID/APOBEC to form 5-hydroxymethyl-Uracil Consistent with the role of Tet in converting 5mC into 5hmC in vivo [13] , Proposed models of Tet-initiated DNA demethylation pathways.…”