Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers.
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.
Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16-18, Leipzig 04107, Germany. hopp@izbi.uni-leipzig.de.
Lydia
L
Hopp
Group of Bioinformatics, Institute of Molecular Biology NAS RA, 7 Hasratyan St, Yerevan 0014, Armenia. l_nersisyan@mb.sci.am.
Lilit
L
Nersisyan
Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16-18, Leipzig 04107, Germany. wirth@izbi.uni-leipzig.de.
Henry
H
Löffler-Wirth
Group of Bioinformatics, Institute of Molecular Biology NAS RA, 7 Hasratyan St, Yerevan 0014, Armenia. aarakelyan@sci.am.|College of Science and Engineering, American University of Armenia, 40 Baghramyan Ave, Yerevan 0019, Armenia. aarakelyan@sci.am.
Arsen
A
Arakelyan
Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16-18, Leipzig 04107, Germany. binder@izbi.uni-leipzig.de.
Hans
H
Binder
B cell maturation; coupling between energy metabolism and epigenetics; methylation of histone-lysine side chains; plasticity of cell function; regulation of gene expression; writers and erasers of epigenetic marks