DNA Sequencing and Fragment Analysis

Posts tagged ‘epigenome’

Epigenetics Research Explores New Cancer Treatments

The genome consists of the entire DNA content in a cell. The human genome consists of approximately 3 billion bases. Many regions of DNA are simple base repeats that do not represent any gene. Some genes are inactive as defined by the epigenome, which plays a major role in cell differentiation. Each type†of cell contains the same copy of the genome. However, genes that are active in one type of cell, such as a skin cell, are not necessarily active in another type of cell, like a liver cell. The difference is found in the methylation of certain genome regions that cause binding to proteins called histones. Genes that lie within bound regions of the genome are silenced, meaning they are inactive.

The Epigenome’s Relation in Cancer

The epigenome can also affect whether certain individuals will develop cancer. People with the genetic potential to develop cancer may not necessarily become sick because the changes may be located in silenced regions of the genome. However, certain external factors can affect the epigenome, thus activating silenced genes. Tobacco, radiation, ultraviolet sunlight and other chemical or radioactive agents can disrupt normal methylation patterns in a group of cells (figure 1). The aging process also plays a role. Throughout life, cells die and are continually replaced. Over time, the number of cell division eventually leads to a loss in methylation for many cells. It is a reason why skin always exposed to sunlight tends to look older than normal skin. Fortunately damage to the epigenome is reversible.

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Cancer Treatments in Epigenetic Studies

Researchers at a number of medical institutions are investigating epigenetic treatments for cancer. Most cancer treatments, like chemotherapy, work by killing cancer cells. However, these treatments may also kill healthy cells. Epigenetic treatments provide a more targeted approach to treating cancer by repairing epigenetic damage. A research team at John Hopkins is working with azacitidine and decitabine. Both medications were found toxic to healthy cells when used in high dosage. However, low dosages of the medications have little effect on healthy cells while repairing epigenetic damage. In vitro studies have shown that specific combinations of both treatments have reduced cultured tumor cells.

Epigenetics as a field has provided a new direction for cancer treatment. It has established that an individual has more control over the potential development of cancer by avoiding factors that cause epigenetic damage.

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Epigenetics: A New Field of Genetic Research

Epigenetics is a relatively new field of research that goes beyond gene expression. It encompasses important areas of research including cell differentiation, cancer and the aging process. Despite complete sequencing of the human genome, there is still much to learn about the complexity of an individual genetic blueprint. Epigenetic research is working to better understand how cells develop into specialized tissue and perform a specified number of functions. The human begins as a single fertilized egg. The egg divides into a growing mass of identical cells. Eventually, individual groups of cells begin to look and act different than other cells. Cell groups develop into tissue and organs. How does this happen when every cell has the same genetic code?

Proximity could play a partial role in cell differentiation. Cells adhering together generally develop into the same tissue. But what boundaries separate each group?

The answers may rest in understanding the epigenome. Epigenetics is a complex field newly emerging in the genetic sciences. Although there is much to learn, there is some basic understanding summarized here.

Histones Play an Important Role in Controlling Gene Expression

DNA is a double stranded molecule that coils around into a helical formation wrapped around histone molecules. Histones are a group of proteins that condense long DNA strands. It is similar to string wrapped around a spool. How tightly DNA is wrapped around the histone molecule determines whether a particular region of DNA is available for transcription and gene expression. Tightly wound DNA is essentially hidden and this region is repressed. Other regions are loosely wound and available for transcription. Transcription is the first step in the protein production process (Figure 1).

Histone molecules are classified into one of five main groups. They are modified in the cell by chemical processes such as methylation, acetylation or other known modifications. Modification is one factor that determines whether DNA is active or repressed. Methylation of certain groups of histones allows genes to be active while others are repressed. However, external factors (like radiation) could effectively influence methylation and activate repressed genes.

Epigenetic Damage is a Cause of Cancer

Let us examine a hypothetical situation in which two individuals have identical genetic content. They are twins. Each individual has identical genes including genes that potentially cause cancer. Why does one individual develop cancer and the other does not?

Research has long understood that cancer could be caused by damage to the DNA making up the genetic blueprint. But external factors can cause damage to DNA leading to cancer as well. Factors that damage the epigenome of an individual can have the same result. An environmental factor like smoking is an example. When cells lose levels of control, they also lose specialization; they de-differentiate. Without such important controls, cells begin to divide uncontrollably into cancer. A better understanding of epigenetic damage has led to new directions in cancer treatment.

Dr. Jean-Pierre Issa explained some general aspects concerning cancer and epigenetic damage during an interview with Nova. See Nova article here.  Epigenetic damage could be related to the aging process. As an individual continues to age, cell division eventually leads to errors in the epigenome. For example, skin constantly exposed to sunlight radiation appears older than normal skin. The aging process is accelerated by stem cells dividing to repair sun damaged skin tissue. The more cells divide, the more the aging processes are accelerated. Dr. Issa utilizes this knowledge in research to determine the apparent age of certain cells.

What Affects the Epigenome?

Current research is attempting to answer this question. There are a number of known environmental conditions that cause damage to the epigenome. Radiation, tobacco and other chemicals have the potential to damage the cellular epigenome. As previously stated, the radiation from excessive sunlight can cause damage to skin tissue. Stem cells divide to repair damaged skin. Damage to skin tissue causes the need for repair and accelerates the aging of stem cells.

Epigenetics is a fascinating new field in the genetic sciences. Understanding factors that affect the epigenome has led medicine into exciting new areas of treatment. This topic is certain to be examined often in the near future.

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