Many scientists are hopeful that studying aberrant epigenetic patterns will help us find promising biomarkers for early diagnosis and prognosis of carcinogenesis. Among such markers, there has recently been heightened interest in 5-hydroxymethylcytosine (5-hmC), which is an enzymatically-modified form of 5-methylcytosine (5-mC). A group of researchers in Europe investigated changes in 5-mC as well as 5-hmC patterns in control and phenobarbital (PB)-treated mice in search for potential biomarkers for the early progression of liver tumorigenesis. Phenobarbital has historically been used to treat convulsions and seizures, but is also known to be a carcinogen in some model systems, such as the mouse model for liver cancer used by the researchers in this report.
The potential use of induced pluripotent stem cells in medicine has the power to completely revolutionize the way physicians treat human diseases. Imagine the possibility of treating diseased or damaged tissue by taking a patient’s own cells from an unaffected tissue, and turning them into healthy cells to replace the bad ones. This idea has been around for years, but has always seemed too far away to consider in reality because it was so difficult to reliably manipulate the cells to induce pluripotency and re-differentiation into the new tissue. The hope of using stem cells for therapeutic purposes has gained renewed attention recently due to the exciting finding by Haruko Obokata, Charles A. Vacanti, and colleagues that differentiated somatic cells can be induced into pluripotency by simply exposing them to extreme external stimuli, such as a low pH buffer.
Over 27 million Americans are estimated to be living with osteoarthritis (OA), a debilitating joint disorder that results from continual loss of cartilage that cushions the bones. OA is accompanied by increased levels of the cytokines Interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) in cartilage cells called chondrocytes. These cytokines have been shown to induce the expression of genes involved in cartilage degradation, and the promoter regions of those genes have been found to be hypomethylated in OA chondrocytes when compared to normal chondrocytes, suggesting epigenetics likely plays a role in OA progression. Active DNA demethylation is mediated by the ten-eleven translocation (TET) enzymes, which oxidize 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), and ultimately, the modification is removed. Interestingly, a recent study by Haseeb et al. found that cultured human primary chondrocytes treated with IL-1β and TNF-α had reduced global 5-hmC levels compared to untreated chondrocytes. Therefore, the authors sought to determine if these reduced 5-hmC levels were a result of IL-1β and TNF-α modulation of the TET1 oxidation pathway and if loss of 5-hmC was seen at specific regions of the genome.
Itching of the eyes and nose, nasal congestion, sneezing, and runny nose are some symptoms of Allergic Rhinitis, better known as hay fever or seasonal allergies, which affects ~30% of people worldwide. In a recent PLOS Genetics publication, scientists from Sweden and the US investigated genome-wide DNA methylation and gene expression changes in CD4+ T-cells from patients with seasonal allergic rhinitis (SAR) and compared them to cells from a healthy control group. Furthermore, the researchers analyzed CD4+ T-cells from the same patient when they were symptom-free (outside of the pollen season) and when they exhibited allergy symptoms. They found that DNA methylation levels, but not changes in gene expression, were significantly different in samples from allergic patients compared to healthy control subjects.
Doctors have long known that a pregnant woman needs adequate levels of folate (also known as vitamin B9) to help prevent serious birth defects. New research in mice now suggests that a father’s level of folate prior to conception also plays a critical role in the baby’s health, through a process termed epigenetic inheritance. Unlike traditional genetic inheritance that involves DNA sequence changes or mutations, epigenetic inheritance is the transmission of additional layers of information (termed epigenetic marks) that affect gene expression and other cellular processes without altering the primary nucleotide sequence. In a recent study, researchers led by Dr. Sarah Kimmins at McGill University in Canada found that a low dietary folate level in male mice produced reproductive difficulties, birth defects, and gene expression abnormalities in their offspring. These reproductive defects were accompanied by changes in DNA methylation levels in sperm cells, suggesting that this epigenetic mark might be responsible. The findings point to dynamic DNA methylation changes in sperm cells as a contributing mechanism to epigenetic inheritance and may therefore lead to a new way of thinking about a father’s contribution to the health of his descendants.