Epigenetic modifications of DNA and histones.
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● Methylation of cytosine residues is associated with gene silencing.
■ Methylation of certain genomic regions is inherited (imprinting), and it is involved in the silencing of one of the two X chromosomes in female (X-inactivation).
● Alterations in methylation can also be acquired, e.g., in cancer cells.
■ Covalent posttranslational modifications of histones play an important role in altering DNA accessibility and chromatin structure and hence in regulating transcription.
● Histones can be reversibly modified in their amino-terminal tails, which protrude from the nucleosome core particle, by acetylation of Iysine, phosphorylation of serine, methylation of Iysine and arginine residues, and sumoylation.
■ Acetylation of histones by histone acetylase 5(HATs), e.g., leads to unwinding of chromatin and accessibility to transcription factors.
● Conversely, deacetylation by histone deacetylases (HDACs) results in a compact chromatin structure and silencing of transcription .