What is the epigenome?
While genomic information is uniform in the different cells
of complex organisms, the epigenome controls the differential expression of
genes in specific cells. The programming of gene expression profiles is therefore
dependent on the epigenome. The epigenome is composed of two modules, a component
that is part of the covalent structure of DNA, methylated cytosines located
in the dinucleotide sequence CG and a noncovalent module. Our understanding
of the noncovalent module of the epigenome the chromatin and its associated
chromatin modifying and remodeling activities is rapidly expanding in recent
years (Strahl and Allis, 2000). It is now becoming clear that modifications
of histones and their tails by acetylation, phosphorylation, and methylation
plays an important role in determining the positioning of nucleosomes on DNA
and the compactness of chromatin. Chromatin structure determines the state
of activity of genes by gating the access of the transcription machinery to
transcriptional regulatory regions. Chromatin structure plays a role in other
genomic activities such as recombination and repai. Changes in chromatin structure
play an important role in the silencing of certain genes in cancer and histone
deacetylase inhibitors have demonstrated anticancer effect.
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