Epigenetics
This refers to changes in DNA and chromatin that affect gene expression
other than those that affect DNA sequence.
Cellular DNA is packaged by wrapping it around histones, a group of
specialized nuclear proteins. The complex is tightly compacted as chromatin. In
order for the DNA code to be read, transcription factors and other proteins
need to physically attach to DNA. Histones act as custodians for this access
and so for gene expression. Histones may be modified by methylation,
acetylation and phosphorylation which can result in increased or decreased gene
expression and so changes in cell phenotype. Epigenetics also includes changes
to DNA itself, such as methylation which regulates gene expression in normal
and tumour tissues. The methylation of cytosine residues to methyl cytosine
results in inhibition of gene transcription. The genes DNMT 3A and B are
involved in the methylation, and TET 1,2,3 and IDH1 and 2 in
the hydroxylation and there- fore breakdown of methylcytosine and restoration
of gene expression
(see Fig. 16.1). These genes are frequently mutated in the myeloid malignancies (see Chapters 13, 15 and 16).
