Page 543 - Veterinary Immunology, 10th Edition

VetBooks.ir Epigenetic Regulation

While every cell in an animal body contains a complete copy of the
genome, they only employ the genes needed for their specific

function. Thus a hepatocyte, for example, only uses those genes
required for liver cell function. How do they do that? Processes that
collectively control gene expression determine which genes are
transcribed in each cell. This is called epigenetic regulation and has
been likened to the software in a computer. Like software, a cell

selects the most appropriate components (genes) for the task at
hand. The importance of epigenetic regulation is well seen in the
regulation of immunoglobulin production. Consider, for example,

how somatic hypermutation and class switch recombination are
regulated.
There are three major mechanisms of epigenetic regulation; DNA
methylation is one. By adding a methyl group to the 5-position in
certain cytosines within a gene, a gene can be turned off.

Conversely demethylation results in gene activation. A second
epigenetic mechanism involves histone modification. DNA in the
nucleus is closely bound to the nuclear proteins called histones.

These histones can be subjected to many chemical modifications
such as methylation, phosphorylation, or acetylation. These histone
modifications are introduced or removed by histone modifying
enzymes. The modifications influence the interactions between the
histones and DNA and as a result may activate or inhibit gene

transcription. The third major epigenetic mechanism involves the
production of microRNAs (miRNAs). These are small, noncoding
RNAs that regulate gene expression by binding to messenger RNAs

and influencing their functions. Collectively, these three epigenetic
mechanisms determine which genes are active and which are
inactive in any given cell type.
Thus B cell activation and differentiation is associated with
genome-wide hypomethylation, an increase in histone acetylation

and the appearance of a specific set of miRNAs. In the case of
immunoglobulin synthesis, class switch recombination and somatic
hypermutation are regulated by all three of these epigenetic

processes. In effect, the production of the appropriate recombinases,

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