10.14:
Epigenetic Regulation
Epigenetic regulation refers to changes in gene expression that can be inherited without changes to the genetic sequence. This occurs during the normal course of development and can also be caused by environmental factors, such as diet, exposure to toxic substances, and stress.
Epigenetic regulation occurs through three main mechanisms: DNA methylation, histone modification, and RNA-based processes.
In DNA methylation, methyl, CH3 groups, are added to specific bases. This alters the ability of regulatory proteins, such as transcription factors, to bind to DNA. Usually preventing the gene from being transcribed.
Histone modification involves adding chemical groups, such as methyl or acetyl groups, to the histone proteins that DNA wraps itself around to form chromatin. These modifications affect how tightly chromatin is folded. Either opening it up, making it more easily transcribed, or condensing it, inhibiting transcription.
Various types of RNA can also have epigenetic effects, including micro-RNAs and small interfering RNAs, which can alter chromatin structure. And messenger RNA, which can be methylated, altering gene translation.
Whatever the mechanism, these modifications are passed down to daughter cells, and sometimes even passed down through generations of individuals, creating long-term phenotypic changes without changes to the genome.
10.14:
Epigenetic Regulation
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]