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Genes 2015, 6(4), 1076-1112; doi:10.3390/genes6041076

Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers

1
Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16–18, Leipzig 04107, Germany
2
Group of Bioinformatics, Institute of Molecular Biology NAS RA, 7 Hasratyan St, Yerevan 0014, Armenia
3
College of Science and Engineering, American University of Armenia, 40 Baghramyan Ave, Yerevan 0019, Armenia
*
Authors to whom correspondence should be addressed.
Academic Editor: Jessica Tyler
Received: 25 May 2015 / Revised: 30 September 2015 / Accepted: 7 October 2015 / Published: 21 October 2015
(This article belongs to the Special Issue Chromatin Dynamics)
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Abstract

We systematically studied the expression of more than fifty histone and DNA (de)methylating enzymes in lymphoma and healthy controls. As a main result, we found that the expression levels of nearly all enzymes become markedly disturbed in lymphoma, suggesting deregulation of large parts of the epigenetic machinery. We discuss the effect of DNA promoter methylation and of transcriptional activity in the context of mutated epigenetic modifiers such as EZH2 and MLL2. As another mechanism, we studied the coupling between the energy metabolism and epigenetics via metabolites that act as cofactors of JmjC-type demethylases. Our study results suggest that Burkitt’s lymphoma and diffuse large B-cell Lymphoma differ by an imbalance of repressive and poised promoters, which is governed predominantly by the activity of methyltransferases and the underrepresentation of demethylases in this regulation. The data further suggest that coupling of epigenetics with the energy metabolism can also be an important factor in lymphomagenesis in the absence of direct mutations of genes in metabolic pathways. Understanding of epigenetic deregulation in lymphoma and possibly in cancers in general must go beyond simple schemes using only a few modes of regulation. View Full-Text
Keywords: writers and erasers of epigenetic marks; methylation of histone-lysine side chains; regulation of gene expression; coupling between energy metabolism and epigenetics; plasticity of cell function; B cell maturation writers and erasers of epigenetic marks; methylation of histone-lysine side chains; regulation of gene expression; coupling between energy metabolism and epigenetics; plasticity of cell function; B cell maturation
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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MDPI and ACS Style

Hopp, L.; Nersisyan, L.; Löffler-Wirth, H.; Arakelyan, A.; Binder, H. Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers. Genes 2015, 6, 1076-1112.

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