De Novo DNA Methyltransferases in Tumorigenesis

Multicellular organisms develop from a single cell, the zygote, that starts to divide and gives rise to daughter cells that subsequently differentiate into specific tissues. The differentiated cells will fulfill specific functions in the body such as the formation of blood, skin or intestine, and become restricted in their potential to develop into various tissues during differentiation. When a cell has differentiated to its final cell type, heritable changes of the DNA are being maintained during cell division, in the form of epigenetic information (described below). Genetic information is stored in the cells in the form of long DNA strands that are folded into chromatin. Chromatin is composed of repeating units of 146 bp of DNA wrapped around a nucleosome. The DNA connecting the nucleosomes is called linker DNA. A nucleosome consists of an octamer of four different histones, two molecules of each histone 2A (H2A), histone 2B (H2B), histone 3 (H3), and histone 4 (H4) (Figure 1). Other histone variants are H3.3, which can be found on active genes, pericentric heterochromatin and telomeres and can replace H3 1; H2A.X is required for efficient DNA double strand break repair, and H2A.Z is reducing chromatin stability and is involved in transcriptional control. Both H2A.X and H2A.Z can replace H2A 2. Histones are important for chromatin organization and regulating gene expression.

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