11.14:
Epigenetic Regulation
Epigenetic changes are modifications in gene expression that can be inherited by daughter cells or passed down through generations without modifications to the genetic sequence.
These modifications can occur during embryo development as a regulatory process, or they can 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 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, to the histone proteins that DNA wraps itself around to form chromatin. These modifications affect chromatin wrapping by opening it up, making it more easily transcribed, or condensing it and inhibiting transcription.
Various types of RNA can also have epigenetic effects, including non-coding RNAs, which recruit the histone modifying enzymes. Additionally, messenger RNA can be methylated, altering translation.
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.