Chromatin Structure and Epigenetics of Tumour Cells: A Review

Eva      Bartova; Jana      Krejci; Roman      Hajek; Andrea      Harnicarova; Stanislav      Kozubek

Abstract

Tumour cells are characterized by karyotype instability, which is accompanied by specific events in the chromatin structure and epigenetic patterns. Epigenetics involves heritable changes in the physical and biochemical state of chromatin, which have no effect on DNA sequences; therefore, changes in the nuclear radial arrangement of chromosomes can also be considered epigenetic events. Nuclear radial distributions of select genomic regions have been studied in many tumour cells and are not influenced by aberrations in chromosome number. On the other hand, genes involved in translocations take up new positions midway between the original coding sequences. The differentiation of leukaemia cells with clinically used agents is often accompanied by nuclear repositioning of tumour-related genes. However, the nuclear rearrangement is cell-type specific and not always associated with changes in the transcriptional activity. Similarly, cell typespecific chromatin structure is observed in tumour cells treated with select cytostatics and inhibitors of epigenetic processes, which have significant influences on the histone code. Chromatin structure and histone modifications were also affected by gamma radiation in leukaemia, multiple myeloma, and solid tumour cells. Interestingly, gamma radiation induced loci proximity, which has been suggested to increase the probability of exchange aberrations typically associated with tumour progression.

Keywords: Tumour cells, chromatin, radiation, DNA methylation, histone modification

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