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11.14: Epigenetic Regulation

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JoVE Core
Cell Biology

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Epigenetic Regulation
 
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11.14: Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.

X-chromosome Inactivation

In most mammals, females have two X chromosomes (XX) while males have an X and a Y chromosome (XY). The X chromosome contains significantly more genes than the Y chromosome. Therefore, to prevent an excess of X chromosome-linked gene expression in females, one of the two X chromosomes is randomly silenced during early development. This process, called X-chromosome inactivation, is regulated by DNA methylation. Scientists have found greater DNA methylation at gene promoter sites on the inactive X chromosome than its active counterpart. DNA methylation prevents the transcription machinery from attaching to the promoter region, thus inhibiting gene transcription.

Epigenetic Dysregulation and Cancer

Epigenetic errors such as modification of the wrong gene or failure to add a chemical group to a particular gene or histone can lead to abnormal gene activity. It is a common cause of genetic disorders, cancers, metabolic disorders, and degenerative disorders. For example, abnormal DNA methylation plays an important role in cancer. The promoter region of most genes contains stretches of cytosine and guanine nucleotides called CpG islands. In healthy cells, CpG islands are not methylated. However, CpG islands in the promoter regions of tumor suppressor genes or cell cycle regulators are excessively methylated in cancer cells. Methylation turns off the expression of these genes, allowing cancer cells to divide rapidly and uncontrollably.

Tags

Keywords: Epigenetic Regulation DNA Methylation X-chromosome Inactivation Epigenetic Dysregulation Cancer CpG Islands Tumor Suppressor Genes Cell Cycle Regulators

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