14.10:
בקרה אפיגנטית
14.10:
בקרה אפיגנטית
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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.
Abnormal DNA methylation plays an important role in cancer. The promoter region of most genes contains stretches of cytosine and guanine nucleotides linked by a phosphate group. These regions are called CpG islands. In healthy cells, CpG islands are not methylated. However, in cancer cells, CpG islands in the promoter regions of tumor suppressor genes or cell cycle regulators are excessively methylated. Methylation turns off the expression of these genes, allowing cancer cells to divide rapidly and uncontrollably.
Suggested Reading
Weinhold, Bob. “Epigenetics: The Science of Change.” Environmental Health Perspectives 114, no. 3 (March 2006): A160–67. [Source]
Gudsnuk, Kathryn, and Frances A. Champagne. “Epigenetic Influence of Stress and the Social Environment.” ILAR Journal 53, no. 3–4 (December 2012): 279–88. [Source]
Simmons, Danielle “Epigenetic influence and disease.” Nature Education 1 no. 1 (2008):6 [Source]
Lim, Derek H. K., and Eamonn R. Maher. “DNA Methylation: A Form of Epigenetic Control of Gene Expression.” The Obstetrician & Gynaecologist 12, no. 1 (2010): 37–42. [Source]